Isaacs appeared in "Black Hawk Down" (2001), Jackie Chan's "The Tuxedo" (2002), as George Darling and Captain Hook in P. J. Hogan's adaptation of "Peter Pan" (2003), and as the voice of Admiral Zhao in of the animated Nickelodeon series "" (2005). He played the leading role of Sir Mark Brydon, the British Ambassador to the United States, in the BBC Four miniseries "The State Within" (2006), for which he was nominated for the Best Performance by an Actor in a Mini-Series or a Motion Picture Made for Television for the 65th Golden Globe Awards. On British television, he also portrayed actor Harry H. Corbett in "The Curse of Steptoe", part of "a season of new one-off dramas for BBC Four revealing the stories behind some of Britain's best loved television entertainers, and their achievements," first broadcast in March 2008. On American television, Isaacs appeared in three episodes of "The West Wing" in 2004, prior to developing his most notable TV serial role, as Michael Caffee in "Brotherhood" (2006–08).