In 1987, the actress took over bartending duties for Shelley Long's Diane Chambers on Cheers, making her debut on the hit NBC series as Rebecca Howe during its sixth season. She remained with the show until its 11th and final season in 1993. Her role of the eccentric bar manager earned her an acting Emmy and Golden Globe in 1991.
Following the success of Cheers, Alley continued to dominate the sit-com genre as the titular character on Veronica's Closet, an NBC show about a newly-single owner of a New York City lingerie company. The show ran for three seasons from 1997 to 2000, with Alley taking home a People's Choice Award for Favorite Female Performer in a New Television Series for her role as Veronica "Ronnie" Chase in 1998.
Playing mom Mollie Jensen, Alley starred opposite of John Travolta in the 1989 comedy. She went on to reprise the role in its 1990 sequel Look Who's Talking Too and 1993 follow-up Look Who's Talking Now.
Alley earned her second Emmy for her role as the mother of a teenager with autism in this 1994 TV film.
Tapping into dark comedy, Alley co-starred alongside Kristen Dunst, Ellen Barkin, Brittany Murphy, Allison Janney, Denise Richards and Amy Adams as Gladys Leeman—the mom to the frontrunner of a small town teen beauty pageant—in the 1999 flick.
Alley wasn't afraid to poke fun at her career in 2005, when she played a fictionalized version of herself on the Showtime comedy. Co-starring Rachael Harris and Bryan Callen, the tongue-in-cheek series centered around Alley's journey to lose weight as part of her television comeback and featured cameos from Rhea Perlman, Mayim Bialik, Leah Remini and Carmen Electra. It ran for one season.
Alley's Diane Barrows was tricked into falling in love with Steve Guttenberg's Roger Callaway in this 1995 comedy starring Mary-Kate and Ashley Olsen.
The 1987 comedy featured Alley as Robin Bishop, a history teacher who falls for Mark Harmon's Freddy Shoop after they're assigned to teach, well, summer school.
The star made her film debut playing Vulcan Starfleet officer Lieutenant Saavik in the 1982 sci-fi flick.
Alley was nominated for an Emmy in 1997 after appearing as Rose Marie Clericuzio in the CBS miniseries. She reprised the role in its 1998 sequel, The Last Don II.