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                                                              EXHIBIT 10.65

                                           January 20, 2003

BY HAND DELIVERY

Christopher D. T. Guiffre
Vice President, General Counsel
   & Secretary
Cubist Pharmaceuticals, Inc.
65 Hayden Avenue
Lexington, MA 02421

     RE: RETENTION LETTER

Dear Chris:

     You are a highly valuable employee of Cubist Pharmaceuticals, Inc.
("Cubist"). Cubist wishes to retain you as an employee, and is therefore willing
to make certain commitments in order to induce you to remain an employee. This
letter will confirm the agreement between you and Cubist ("Agreement") in that
regard. The Agreement is as follows:

     1.   DEFINITIONS. For the purposes of this Agreement, the following
          definitions apply:

          (a)  "Cause" means: (i) you commit of an act of fraud or
               misrepresentation in connection with your employment; (ii) you
               are convicted of, or plead nolo contendere to, a felony or a
               crime involving moral turpitude; (iii) you breach any material
               obligation under your Proprietary Information and Inventions
               Agreement; (iv) you engage in substantial or continuing
               inattention to or neglect of your duties and responsibilities
               reasonably assigned to you by Cubist; or (v) you engage in
               substantial or continuing acts to the detriment of Cubist or you
               engage in substantial or continuing acts inconsistent with
               Cubist's policies or practices.

          (b)  "Good Reason" means: (i) the failure of Cubist to employ you in
               your current or a substantially similar position such that your
               duties and responsibilities are materially diminished without
               your consent; (ii) a reduction in your aggregate base salary and
               potential bonus without your consent (unless such reduction is in
               connection with a proportional reduction in compensation to all
               or substantially all of Cubist's employees); or (iii) a
               relocation of your primary place of employment more than 20 miles
               from your current site of employment without your consent.

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          (c)  a "Change of Control" occurs: (i) when any person or entity other
               than Cubist or one of its subsidiaries becomes the owner of fifty
               percent (50%) or more of Cubist's common stock or (ii) upon the
               effective date of an agreement of acquisition, merger, or
               consolidation that has been approved by Cubist's stockholders and
               that contemplates that all or substantially all of the business
               and/or assets of Cubist shall be owned or otherwise controlled by
               another person or entity upon the effective date of such
               agreement.

     2.   SEVERANCE. In the event that your employment is terminated by Cubist
          for any reason other than for Cause, or by you for Good Reason, then,
          within five (5) days of the date of your termination, Cubist shall
          make a one-time, lump-sum payment to you equal to twelve (12) months
          of your then-current base salary.

     3.   WITHHOLDING. All payments made by Cubist under this Agreement shall be
          reduced by any tax or other amounts required to be withheld by Cubist
          under applicable law.

     4.   MEDICAL AND DENTAL BENEFITS. In the event that your employment is
          terminated by Cubist for any reason other than for Cause, or by you
          for Good Reason, then Cubist will maintain your medical and dental
          insurance coverage for a period of up to twelve (12) months after the
          month in which your employment terminates, provided that you pay the
          employee portion for such coverage by making a payment to Cubist
          during the first five (5) days of any month in which you elect to
          continue such coverage. Except for any right you have to continue
          participation in Cubist's group health and dental plans as provided
          herein or under the federal law known as "COBRA," all employee
          benefits shall terminate in accordance with the terms of the
          applicable benefit plans as of the date of termination of your
          employment.

     5.   ACCELERATION OF OPTIONS. In the event that, within twenty-four (24)
          months after a Change of Control, your employment is terminated either
          (i) by Cubist for any reason other than for Cause or (ii) by you for
          Good Reason, then all outstanding unvested stock options and/or
          restricted stock awards granted to you under any Cubist stock option
          plan prior to the Change of Control shall become exercisable and
          vested in full, and all restrictions thereon shall lapse,
          notwithstanding any vesting schedule or other provisions to the
          contrary in the agreements evidencing such options or awards, and
          Cubist and you hereby agree that such stock option agreements and
          restricted stock awards are hereby, and will be deemed to be, amended
          to give effect to this provision.

     6.   NO CONTRACT OF EMPLOYMENT. This Agreement is not a contract of
          employment for a specific term, and your employment is "At Will" and
          may be terminated by Cubist at any time.

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     7.   EMPLOYEE RELEASE. Any obligation of Cubist to provide you severance
          payments or other benefits under this Agreement is expressly
          conditioned upon your reviewing and signing (and not revoking during
          any applicable revocation period) a general release of claims in a
          form reasonably satisfactory to Cubist. Cubist shall provide you with
          the general release promptly after the date on which you give or
          receive, as the case may be, notice of termination of your employment.

     8.   ASSIGNMENT. You shall not make any assignment of this Agreement or any
          interest in it, by operation of law or otherwise, without the prior
          written consent of Cubist. Cubist may assign its rights and
          obligations under this Agreement without your consent. This Agreement
          shall inure to the benefit of and be binding upon you and Cubist, and
          each of our respective successors, executors, administrators, heirs
          and permitted assigns.

     9.   SEVERABILITY. If any portion or provision of this Agreement shall to
          any extent be declared illegal or unenforceable by a court of
          competent jurisdiction, then the remainder of this Agreement, or the
          application of such portion or provision in circumstances other than
          those as to which it is so declared illegal or unenforceable, shall
          not be affected thereby, and each portion and provision hereof shall
          be valid and enforceable to the fullest extent permitted by law.

     10.  MISCELLANEOUS. This Agreement sets forth the entire agreement between
          you and Cubist in connection with the subject matter hereof, and
          replaces all prior and contemporaneous communications, agreements and
          understandings, written or oral, with respect to the subject matter
          hereof with the exception of your obligations set forth in your
          Proprietary Information and Inventions Agreement with Cubist, which
          obligations shall remain in full force and effect. In consideration of
          the benefits provided to you hereunder, you agree that, in the event
          of your termination from Cubist, such benefits shall be in complete
          satisfaction of any and all obligations that Cubist may have to you.
          This Agreement may not be modified or amended, and no breach shall be
          deemed to be waived, unless agreed to in writing by you and an
          expressly authorized representative of Cubist. This Agreement may be
          executed in two counterparts, each of which shall be an original and
          all of which together shall constitute one and the same instrument.
          This Agreement shall be governed by the laws of the Commonwealth of
          Massachusetts, without regard to its conflicts of laws principles, and
          all disputes hereunder shall be adjudicated in the courts of the
          Commonwealth of Massachusetts, to whose personal jurisdiction you
          hereby consent.

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If the foregoing is acceptable to you, please sign both copies of this letter in
the space provided, at which time this letter will take effect as a binding
agreement between you and Cubist. Please keep one original for your records and
return one original to me.

                                        Cubist Pharmaceuticals, Inc.

                                        By: /s/ Scott M. Rocklage
                                            ------------------------------------
                                                Scott M. Rocklage, Ph.D.
                                                Chairman and CEO

Accepted and Agreed:

By: /s/ Christopher D.T. Guiffre
    ---------------------------------
Name: Christopher D.T. Guiffre
Date:

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                                                              EXHIBIT 10.66

                                           February 25, 2003

BY HAND DELIVERY

Dr. Scott M. Rocklage
Chairman & CEO
Cubist Pharmaceuticals, Inc.
65 Hayden Avenue
Lexington, MA 02421

     RE:  TRANSITION AGREEMENT

Dear Scott:

     This letter agreement documents the transition agreement between you and
Cubist Pharmaceuticals, Inc. ("Cubist" or the "Company") regarding your
transition from your dual position as Cubist's Chairman of the Board of
Directors ("Chairman") and CEO to the position of Chairman. The Cubist Board of
Directors (the "Board") highly commends you for your many years of dedicated and
outstanding service to the Company, including the successful filing of its first
NDA, and wishes to recognize and reward you for those important contributions.
As agreed by you and the Board, it is in the best interest of the Company to
retain your services as Chairman and to appoint me to the position of President
& CEO, upon the following terms and conditions:

     1.   ANNOUNCEMENT OF TRANSITION.

     The Company will promptly upon execution of this Agreement announce your
planned resignation as CEO, your continuation as Chairman, and my planned
appointment as President & CEO.

     2.   EFFECTIVE DATE OF TRANSITION AS CEO.

     Your resignation as CEO will be effective immediately prior to the
Company's Annual Meeting of Stockholders on June 10, 2003, as evidenced by your
resignation letter to Dr. David Martin, Chairman of the Compensation Committee,
executed this day and in the form attached as EXHIBIT A. At such time, I will be
appointed President & CEO of the Company and will be introduced to the Company
and its stockholders as such at the Annual Meeting.

     3.   EMPLOYMENT.

     You will remain Chairman and an employee of the Company through
December 31, 2003, and you will receive your full salary and bonus through that
date. The last day of your employment with the Company will be December 31,
2003.

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                                       -2-
     4.   OTHER COMPENSATION.

     Subject to Section 9 of this Agreement, on January 5, 2004, you will
receive a one-time Special Recognition Award in an amount equal to $440,000, in
recognition of your many and significant contributions to the Company since June
of 1994.

     After January 5, 2004, you will receive no compensation other than
compensation paid to the Company's outside Directors, as long as you are serving
as a Director or as Chairman. As long as you serve as Chairman your compensation
package shall be two times what other Directors earn, both in terms of cash
compensation and options.

     5.   STOCK OPTIONS.

     All then unvested stock options granted to you as an employee of the
Company will vest on December 31, 2003, and will be exercisable until
December 31, 2006, except to the extent that options have expired by their terms
before that date.

     6.   BENEFITS.

     To the maximum extent possible, the Company will continue your
participation in all of its health benefits until the later of (a) December 31,
2006 or (b) until you are no longer a member of the Board. Thereafter, assuming
that COBRA benefit legislation (or its equivalent) then exists in its present
form, you will be eligible for COBRA benefits (or benefits provided under
equivalent legislation).

     7.   CONTINUATION AS CHAIRMAN AND/OR DIRECTOR.

     The Board believes that it is in the best interest of the Company for you
to continue to serve as Chairman and a Director through December 31, 2003 ("year
end"). You agree to continue to serve in those capacities through year end.
Although you have tendered your resignations as of year end, you also agree to
consider serving as Chairman (and a Director) after that date if requested to do
so by the Board.

     8.   NON-COMPETE.

     You agree that, during the period of your employment by the Company as CEO,
you will not, without the Company's express written consent, engage in any
employment or business activity other than for the Company. In view of the
unique nature of the business of the Company and the need of the Company to
maintain its competitive advantage in the industry, you agree that for a period
of three (3) years after the termination of your tenure as CEO of the Company
for any reason whatsoever, you shall not directly or indirectly, within the
United States of America or its territories or possessions or within any other
part of the world (i) engage in, (ii) own an interest in (except that you may
own less than 5% of publicly traded companies) (iii) be employed by or consult
for or act as an advisor to any person or entity which engages in or (iv)
otherwise participate in any way in, any activity which competes with the
Business (as

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defined below). During the term of your tenure as CEO of the Company and for a
period of three (3) years thereafter, you shall not solicit or arrange to have
any other person or entity solicit any person or entity engaged by the Company
as an employee, customer, supplier, or consultant or advisor to the Company to
terminate such party's relationship with the Company. The time periods provided
for in this Section 8 shall be extended for a period of time equal to any period
of time in which you shall be in violation of any provision of this Section 8.
For purposes of this Section 8 the term "Business" shall mean: (i) the current
business of the Company, defined as the research, development, manufacture, use,
patenting, promotion, distribution, sale and license of treatments, in-vitro
diagnosis and therapies related to microbial diseases, and (ii) any other
business or businesses conducted by the Company at any time during your tenure
as an employee of the Company.

     The Company shall have the right to enforce this Agreement and any of its
provisions by injunction, specific performance or other equitable relief,
without bond, and without prejudice to any other rights and remedies that the
Company may have for a breach of this Agreement. You waive the claim or defense
that the Company has an adequate remedy at law. You shall not, in any action or
proceeding to enforce any of the provisions of this Agreement, assert the claim
or defense that such an adequate remedy at law exists.

     9.   GENERAL RELEASE.

     Any obligation of Cubist to provide you the Special Recognition Award or
other benefits under this Agreement after the termination of your employment is
expressly conditioned upon your signing and delivering to the Company by
December 26, 2003 (and not revoking during any applicable revocation period) a
general release of claims in the form attached as EXHIBIT B.

     10.  JURISDICTION AND VENUE; WAIVER OF JURY TRIAL; GOVERNING LAW.

     This Agreement will be governed by and construed in accordance with the
laws of the Commonwealth of Massachusetts. In case of any dispute hereunder, the
parties will submit to the exclusive jurisdiction and venue of any court of
competent jurisdiction sitting in Middlesex County, Massachusetts, and will
comply with all requirements necessary to give such court jurisdiction over the
parties and the controversy. EACH PARTY HEREBY WAIVES ANY RIGHT TO A JURY TRIAL
AND TO CLAIM OR RECOVER PUNITIVE DAMAGES WITH RESPECT TO THIS AGREEMENT.

     This Agreement will be publicly filed with the Company's Exchange Act
filings. The Board has adopted a resolution authorizing and instructing me to
execute this Agreement on behalf of Cubist. If the terms herein are acceptable
to you, please execute both originals, keep one for your records, and return one
to me.

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                                       -4-

     Thank you for your continued commitment to Cubist. I look forward to
working with you in your new role as Chairman.

                                     Very truly yours,

                                     /s/ Michael W. Bonney
                                     -----------------------------------
                                     Michael W. Bonney
                                     President & COO

ACCEPTED AND AGREED

By: /s/ Scott M. Rocklage
   ------------------------------
   Scott M. Rocklage, Ph.D.

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