Kirstie Alley was born in Wichita, Kansas, where she was a bit of a hell-raiser. Alley attended Kansas State University, but transferred to the University of Kansas before dropping out to be an actress. During this time she was briefly married to Bob Alley (1974-1977). In 1978, Alley moved to Hollywood, and her first TV appearance was as a contestant on Match Game in 1979, followed by an appearance on another game show, Password Plus, in 1980.

Alley's film career got a major kickoff in the early 80's, when she was cast as Vulcan officer Saavik in the blockbuster Star Trek II: The Wrath of Kahn. Other film work included Runaway and Blind Date. Alley turned down reprising the role of Saavik in Star Trek III: The Search for Spock, because she didn't want to be typecast. She resumed her TV work with appearances on The Love Boat, a co-starring role in the short-lived TV series Masquerade and a starring role in the ABC mini-series North & South.

In 1984 TV director/producer James Burrows saw Alley in a theatrical production of Cat on a Hot Tin Roof in the role of Maggie the Cat and was impressed by her performance, as he was with her turn in the movie Summer School. When it came time to cast a new female lead on Cheers after Shelley Long's departure, Burrows remembered the actress and had her audition for the role of the career-minded bar manager Rebecca Howe. Alley received two Emmy Awards (1991, 1994) and a Golden Globe Award (1991) for her comic portrayal of the nutty neurotic.

Alley continued to star in movies during her run on Cheers. Film work at this time included Look Who's Talking, Madhouse, Look Who's Talking Too and Look Who's Talking Now. When Cheers wrapped in 1993, Alley disappeared from the screen for a while. In 1997, Woody Allen cast her in a somewhat dramatic role in Deconstructing Harry. In that same year she reappeared on TV as the star and producer of the sitcom Veronica's Closet. Alley is the only Cheers regular who never reprised her role on spin-off series Frasier.

Lately, Alley has made something of a career as a TV spokesperson for Pier One Imports (Alley had been an interior decorator prior to acting) and Jenny Craig Weight Loss Centers (a dramatic weight gain made her a cause célèbre, even garnering her a short-lived series on Showtime, Fat Actress, a semi-autobiographical series about an overweight middle-aged actress).

Alley was married to actor/director Parker Stevenson for 14 years (they divorced in 1997), and together they have two children.