- 2008: Played the central character of a woman whose husband has left her in Diane English's female ensemble "The Women," a remake of the 1936 play by Clare Boothe Luce
- 2007: Cast as a struggling mother of two daughters in Jonathan Kasdan's directorial debut "In the Land of Women"
- 2004: Portrayed the first female boxing manager in the film "Against the Ropes"
- 2003: Directed by Jane Campion in the erotic thriller "In the Cut"
- 2001: Starred opposite Hugh Jackman in the romantic comedy "Kate & Leopold"
- 2000: Began an off-screen affair with co-star Russell Crowe when they starred together in Taylor Hackford's "Proof of Life"
- 1998: Re-teamed with Quaid for the contemporary remake of "D.O.A."
- 1998: Third teaming with Tom Hanks and writer/director Ephron in "You've Got Mail"; received a Golden Globe nomination for Best Actress
- 1998: Had dramatic supporting role in Anthony Drazan's "Hurlyburly"
- 1998: Played a pragmatic heart surgeon opposite Nicholas Cage in "City of Angels," a remake of Wim Wenders' "Wings of Desire"
- 1997: Provided the speaking voice of the title character in the animated feature "Anastasia"
- 1997: Attempted to change her screen persona by playing a cynical photographer in "Addicted to Love"
- 1996: Portrayed an Army captain under investigation in the Persian Gulf drama "Courage Under Fire"
- 1995: Renewed first-look production deal with FOX; Kathryn Galen replaced by Nina Sadowsky as president of Prufrock Pictures
- 1995: Feature producing debut, "French Kiss" (also starred)
- 1994: Offered a fine dramatic turn as an alcoholic wife and mother in "When a Man Loves a Woman"; received a SAG nomination for Best Female Lead
- 1993: Formed Fandango Films (renamed Prufrock Pictures), a production company based at FOX with business partner Kathryn Galan
- 1993: Re-teamed with husband, Dennis Quaid for the dramatic "Flesh and Bone"
- 1993: Again paired with Tom Hanks in the hit romantic comedy "Sleepless in Seattle"; second collaboration with writer/director Ephron; received a Golden Globe nomination for Best Actress
- 1992: Starred opposite Alec Baldwin in Craig Lucas' feature adaptation of his play, "Prelude to a Kiss"
- 1991: Portrayed Pamela Morrison in Oliver Stone's biopic "The Doors"
- 1990: First screen pairing with Tom Hanks in "Joe Versus the Volcano"; played multiple roles
- 1989: Breakthrough lead role opposite Billy Crystal in "When Harry Met Sally..."; film written by Nora Ephron and directed by Rob Reiner; received a Golden Globe nomination for Best Actress
- 1987: First oncreen pairing with future husband Dennis Quaid, "Innerspace"
- 1986: First adult role in features, "Top Gun"; played wife of naval aviator Nick 'Goose' Bradshaw (played by Anthony Edwards)
- 1985: Appeared in Richard Fleischer's "Amityville 3D"
- 1982: Cast in a regular role as Betsy Stewart in the CBS daytime drama "As the World Turns"
- 1982: TV debut in the ABC Afterschool Special, "Amy and the Angel"
- 1981: Made film debut in George Cukor's "Rich and Famous" as Candice Bergen's daughter
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