But her biggest success to date came with the hit comedy "Pretty Woman" (1990), which Ziskin executive produced for Touchstone. The following year was a let-down for Ziskin and Touchstone alike, with "What About Bob?" and "The Doctor" failing to find audiences. A switch to Columbia resulted in Stephen Frears' "Hero" (1992), a loose remake of 1941's "Meet John Doe", for which Ziskin both produced and supplied the story. She directed her first short film in 1994, "Oh, What a Day! 1914" and produced the marvelous Nicole Kidman tour-de-force "To Die For" (1995), under the banner of Laura Ziskin Productions.
By the time that last film was in release, however, she had been appointed president of Fox 2000, one of several off-shoots 20th-Century-Fox developed to speed up their production and distribution. Since the formation of Fox 2000, Ziskin rounded up an impressive number of hot directors (i.e., David Fincher, John N Smith, Carl Franklin) and writers (e.g., Jon Robin Baitz, David Ives, Lisa Loomer), though most of their film projects never got beyond the development process. Among those released were Edward Zwick's Gulf War drama "Courage Under Fire" and the romantic comedy "One Fine Day" (both 1996) and Pat O'Connor's "Inventing the Abbotts" and the big-budget disaster film "Volcano" (both 1997). In 1996, Fox 2000 also pooled resources with Fox Searchlight to distribute Anthony Minghella's acclaimed, award-winning "The English Patient".
After nearly five years on the job, Ziskin resigned from Fox 2000 in November 1999 and within a month had a production deal at Columbia. After being tapped to serve as the first solo female producer of an Academy Awards telecast in 2002, she returned to the big screen with the highly anticipated feature version of "Spider-Man".