<PAGE>

     As filed with the Securities and Exchange Commission on August 29, 2000
                                                           Registration No. 333-
================================================================================

                       SECURITIES AND EXCHANGE COMMISSION
                             Washington, D.C. 20549

                         ------------------------------

                                    FORM S-8
                             REGISTRATION STATEMENT
                                      UNDER
                           THE SECURITIES ACT OF 1933

                         ------------------------------

                              PHARSIGHT CORPORATION
             (Exact name of registrant as specified in its charter)


          Delaware                                     77-0401273
   (STATE OF INCORPORATION)                (I.R.S. EMPLOYER IDENTIFICATION NO.)

                         ------------------------------

                       800 West El Camino Real, Suite 200
                         Mountain View, California 94040
                                 (650) 314-3800
                    (ADDRESS OF PRINCIPAL EXECUTIVE OFFICES)


                         ------------------------------

                           2000 Equity Incentive Plan
                    2000 CEO Non-Qualified Stock Option Plan
                             1997 Stock Option Plan
                             1995 Stock Option Plan
                            (FULL TITLE OF THE PLANS)

                                Arthur H. Reidel
                      President and Chief Executive Officer
                              Pharsight Corporation
                       800 West El Camino Real, Suite 200
                         Mountain View, California 94040
                                 (650) 314-3800
            (NAME, ADDRESS, INCLUDING ZIP CODE, AND TELEPHONE NUMBER,
                   INCLUDING AREA CODE, OF AGENT FOR SERVICE)

                         ------------------------------

                                   Copies to:
                              Brett D. White, Esq.
                           Thomas L. MacMitchell, Esq.
                               COOLEY GODWARD LLP
                              Five Palo Alto Square
                               3000 El Camino Real
                              Palo Alto, California
                                 (650) 843-5000

                         ------------------------------

                         CALCULATION OF REGISTRATION FEE
<TABLE>
<CAPTION>
============================ ========================= ========================== ========================= ========================
                                                           Proposed Maximum           Proposed Maximum
    Title of Securities                                        Offering                  Aggregate                 Amount of
     to be Registered        Amount to be Registered      Price per Share (1)        Offering Price (1)         Registration Fee
---------------------------- ------------------------- -------------------------- ------------------------- ------------------------
<S>                              <C>                            <C>                     <C>                         <C>
  Common Stock, par value        6,932,905 shares               $8.155                  $44,703,569                 $11,802
     $0.001 per share
============================ ========================= ========================== ========================= ========================
</TABLE>

(1)      Estimated solely for the purpose of calculating the amount of the
         registration fee pursuant to Rule 457(h). The price per share and
         aggregate offering price are based upon (a) the weighted average
         exercise price for options granted pursuant to the Registrant's 2000
         CEO Non-Qualified Stock Option Plan, 1997 Stock Option Plan and 1995
         Stock Option Plan and (b) the average of the high and low prices of
         Registrant's Common Stock on August 24, 2000 as reported on the Nasdaq
         National Market.


The chart below details the calculations of the registration fee:

<TABLE>
<CAPTION>
---------------------------------------- -------------------------------- ---------------------- ---------------------
                                                                           OFFERING PRICE PER     AGGREGATE OFFERING
              SECURITIES                        NUMBER OF SHARES                  SHARE                 PRICE
---------------------------------------- -------------------------------- ---------------------- ---------------------
<S>                                      <C>                              <C>                    <C>
Shares issuable pursuant to the 2000
CEO Non-Qualified Stock Option Plan,
the 1997 Stock Option Plan and the
1995 Stock Option Plan for which
options have been granted                        2,932,905                     $4.12(1)(a)                $12,083,569
---------------------------------------- -------------------------------- ---------------------- ---------------------
Shares issuable pursuant to the 2000
Equity Incentive Plan for which
options have not been granted                    4,000,000                    $8.155(1)(b)                $32,620,000
---------------------------------------- -------------------------------- ---------------------- ---------------------
</TABLE>


<PAGE>

                                     PART II

               INFORMATION REQUIRED IN THE REGISTRATION STATEMENT

ITEM 3.  INCORPORATION OF DOCUMENTS BY REFERENCE

         The following documents filed by Pharsight Corporation (the
"Registrant") with the Securities and Exchange Commission are incorporated by
reference into this Registration Statement:

         (a) The Registrant's latest prospectus filed pursuant to Rule 424(b)
under the Securities Act of 1933, as amended (the "Act"), on August 9, 2000.

         (b) All other reports filed pursuant to Sections 13(a) or 15(d) of the
Exchange Act since the end of the fiscal year covered by the annual reports, the
prospectus or the registration statement referred to in (a) above.

         (c) The description of the Registrant's Common Stock which is contained
in a registration statement filed on August 4, 2000 under the Securities
Exchange Act of 1934, as amended (the "Exchange Act"), including any amendment
or report filed for the purpose of updating such description.

         All reports and other documents subsequently filed by the Registrant
pursuant to Sections 13(a), 13(c), 14 and 15(d) of the Exchange Act prior to the
filing of a post-effective amendment which indicates that all securities offered
have been sold or which deregisters all securities then remaining unsold, shall
be deemed to be incorporated by reference herein and to be a part of this
registration statement from the date of the filing of such reports and
documents.


ITEM 4.  DESCRIPTION OF SECURITIES

         Not Applicable.


ITEM 5.  INTERESTS OF NAMED EXPERTS AND COUNSEL

         As of August 25, 2000, GC&H Investments, an investment partnership
composed of current and former partners and associates of Cooley Godward LLP,
owns 21,274 shares of the Registrant's Common Stock.


ITEM 6.  INDEMNIFICATION OF DIRECTORS AND OFFICERS

         Section 145 of the Delaware General Corporation Law, permits
indemnification of officers, directors, and other corporate agents under certain
circumstances and subject to certain limitations. The Registrant's Amended and
Restated Certificate of Incorporation and Bylaws provide that the Registrant
shall indemnify its directors, officers, employees and agents to the full extent
permitted by the Delaware General Corporation Law, including circumstances in
which indemnification is otherwise discretionary under Delaware law. In
addition, the Registrant has entered into separate indemnification agreements
with its directors and executive officers which require the Registrant, among
other things, to indemnify them against certain liabilities which may arise by
reason of their status or service (other than liabilities arising from acts or
omissions not in good faith or willful misconduct).

         These indemnification provisions and the indemnification agreements
entered into between the Registrant and its executive officers and directors may
be sufficiently broad to permit indemnification of the Registrant's executive
officers and directors for liabilities (including reimbursement of expenses
incurred) arising under the Act.

ITEM 7.  EXEMPTION FROM REGISTRATION CLAIMED

         Not Applicable.


ITEM 8.  EXHIBITS

                                       1.
<PAGE>

EXHIBIT
NUMBER

     5.1       Opinion of Cooley Godward LLP

    23.1       Consent of Ernst & Young LLP, independent auditors

    23.2       Consent of Cooley Godward LLP is contained in Exhibit 5.1 to this
               Registration Statement

    24         Power of Attorney is contained on the signature pages.

    99.1*      2000 Equity Incentive Plan

    99.2*      2000 CEO Non-Qualified Stock Option Plan

    99.3*      1997 Stock Option Plan

    99.4*      1995 Stock Option Plan

*  Filed as an exhibit to the Registrant's Registration Statement on Form S-1
(No. 333-34896).

ITEM 9.  UNDERTAKINGS

(a)      The undersigned registrant hereby undertakes:

         (1)   To file, during any period in which offers or sales are being
made, a post-effective amendment to this registration statement:

               (i)   To include any prospectus required by section 10(a)(3)
of the Securities Act;

               (ii)  To reflect in the prospectus any facts or events arising
after the effective date of the registration statement (or the most recent
post-effective amendment thereof) which, individually or in the aggregate,
represent a fundamental change in the information set forth in the
registration statement. Notwithstanding the foregoing, any increase or
decrease in volume of securities offered (if the total dollar value of
securities offered would not exceed that which was registered) and any
deviation from the low or high end of the estimated maximum offering range
may be reflected in the form of prospectus filed with the Commission pursuant
to Rule 424(b) (Section 230.424(b) of this chapter) if, in the aggregate, the
changes in volume and price represent no more than a 20% change in the
maximum aggregate offering price set forth in the "Calculation of
Registration Fee" table in the effective registration statement.

               (iii) To include any material information with respect to the
plan of distribution not previously disclosed in the registration statement
or any material change to such information in the registration statement;

         PROVIDED, HOWEVER, that paragraphs (a)(i) and (a)(ii) do not apply
if the information required to be included in a post-effective amendment by
those paragraphs is contained in periodic reports filed by the issuer
pursuant to section 13 or section 15(d) of the Exchange Act that are
incorporated by reference herein.

         (2)   That, for the purpose of determining any liability under the
Securities Act, each such post-effective amendment shall be deemed to be a
new registration statement relating to the securities offered herein, and the
offering of such securities at that time shall be deemed to be the initial
bona fide offering thereof.

         (3)   To remove from registration by means of a post-effective
amendment any of the securities being registered which remain unsold at the
termination of the offering.

                                       2.
<PAGE>

(b)  The undersigned registrant hereby undertakes that, for purposes of
determining any liability under the Securities Act, each filing of the
registrant's annual report pursuant to Section 13(a) or Section 15(d) of the
Exchange Act (and, where applicable, each filing of an employee benefit plan's
annual report pursuant to section 15(d) of the Exchange Act) that is
incorporated by reference in the Registration Statement shall be deemed to be a
new registration statement relating to the securities offered herein, and the
offering of such securities at that time shall be deemed to be the initial bona
fide offering thereof.

(c)  Insofar as indemnification for liabilities arising under the Securities Act
may be permitted to directors, officers and controlling persons of the
registrant pursuant to the foregoing provisions, or otherwise, the registrant
has been advised that in the opinion of the Securities and Exchange Commission
such indemnification is against public policy as expressed in the Securities Act
and is, therefore, unenforceable. In the event that a claim for indemnification
against such liabilities (other than the payment by the registrant of expenses
incurred or paid by a director, officer or controlling person of the registrant
in the successful defense of any action, suit or proceeding) is asserted by such
director, officer or controlling person in connection with the securities being
registered, the registrant will, unless in the opinion of its counsel the matter
has been settled by controlling precedent, submit to a court of appropriate
jurisdiction the question whether such indemnification by it is against public
policy as expressed in the Securities Act and will be governed by the final
adjudication of such issue.


                                       3.
<PAGE>

                                   SIGNATURES

         Pursuant to the requirements of the Securities Act of 1933, as amended,
the Registrant certifies that it has reasonable grounds to believe that it meets
all of the requirements for filing on Form S-8 and has duly caused this
Registration Statement to be signed on its behalf by the undersigned, thereunto
duly authorized, in the City of Mountain View, State of California, on
August 29, 2000.


                                          PHARSIGHT CORPORATION


                                          /s/  Robin A. Kehoe
                                          --------------------------------------
                                          By:     Robin A. Kehoe
                                          Title:  Senior Vice President, Finance
                                                  and Chief Financial Officer


                                POWER OF ATTORNEY

         KNOW ALL PERSONS BY THESE PRESENTS, that each person whose signature
appears below constitutes and appoints Arthur H. Reidel and Robin A. Kehoe, and
each or any one of them, his or her true and lawful attorney-in-fact and agent,
with full power of substitution and resubstitution, for him or her and in his or
her name, place and stead, in any and all capacities, to sign any and all
amendments (including post-effective amendments) to this Registration Statement,
and to file the same, with all exhibits thereto, and other documents in
connection therewith, with the Securities and Exchange Commission, granting unto
said attorneys-in-fact and agents, and each of them, full power and authority to
do and perform each and every act and thing requisite and necessary to be done
in connection therewith, as fully to all intents and purposes as he or she might
or could do in person, hereby ratifying and confirming all that said
attorneys-in-fact and agents, or any of them, or their or his or her substitutes
or substitute, may lawfully do or cause to be done by virtue hereof.

         Pursuant to the requirements of the Securities Act of 1933, this
Registration Statement has been signed by the following persons in the
capacities and on the dates indicated.

<TABLE>
<CAPTION>
                SIGNATURE                                                TITLE                                 DATE

<S>                                                         <C>                                          <C>
                                                             President, Chief Executive Officer and       August 29, 2000
/s/  Arthur H. Reidel                                        Chairman of the Board
--------------------------------------------
                 (ARTHUR H. REIDEL)

/s/  Robin A. Kehoe                                          Senior Vice President, Finance and           August 29, 2000
--------------------------------------------                 Chief Financial Officer (Principal
                  (ROBIN A. KEHOE)                           Financial and Accounting Officer)

                                                             Director
--------------------------------------------
                 (STEVEN D. BROOKS)

/s/  Philippe O. Chambon                                     Director                                     August 29, 2000
--------------------------------------------
         (PHILIPPE O. CHAMBON, M.D., Ph.D.)

/s/  Robert B. Chess                                         Director                                     August 29, 2000
--------------------------------------------
                  (ROBERT B. CHESS)

                                       4.
<PAGE>

/s/  Douglas E. Kelly                                        Director                                     August 29, 2000
--------------------------------------------
              (DOUGLAS E. KELLY, M.D.)

                                                             Director
--------------------------------------------
                  (DEAN O. MORTON)

                                                             Director
--------------------------------------------
                (GARY L. NEIL, PH.D.)

/s/  W. Ferrell Sanders                                      Director                                     August 29, 2000
--------------------------------------------
                (W. FERRELL SANDERS)
</TABLE>


                                       5.
<PAGE>

                                  EXHIBIT INDEX


EXHIBIT
NUMBER

     5.1       Opinion of Cooley Godward LLP

    23.1       Consent of Ernst & Young LLP, independent auditors

    23.2       Consent of Cooley Godward LLP is contained in Exhibit 5.1 to this
               Registration Statement

    24         Power of Attorney is contained on the signature pages.

    99.1*      2000 Equity Incentive Plan

    99.2*      2000 CEO Non-Qualified Stock Option Plan

    99.3*      1997 Stock Option Plan

    99.4*      1995 Stock Option Plan

*  Filed as an exhibit to the Registrant's Registration Statement on Form S-1
(No. 333-34896).