By 1989, Kudrow had begun to make inroads as a guest actor on TV sitcoms, beginning with an appearance as a dizzy acting classmate of bartender Woody (Woody Harrelson) in an episode of "Cheers". Roles on other shows such as the final episode of "Newhart", "Coach" and a recurring part on "Bob" followed. The now bottle blonde Kudrow established her TV presence in the recurring role of the bumbling space cadet waitress Ursula on NBC's "Mad About You". After being fired from the role of radio producer Roz during the shooting of the pilot of "Frasier", she bounced back by landing the star-making part of Phoebe Buffay, the loopy would-be folksinger and twin to Ursula, on the NBC sitcom "Friends" (1994-2004). Over the course of the show's run, her character matured by seeking her birth mother and acting as surrogate mother to her brother. For her efforts, the actress received the Emmy Award as Outstanding Supporting Actress in a Comedy Series in 1998 and earned additional nominations in 1995, 1997, 1999, 2000 and 2001.

Kudrow nearly made her big screen debut in Sandra Locke's "Impulse" (1990) but her role ended on the proverbial cutting room floor. Her first released film was "The Unborn" (1991) and she subsequently appeared in a handful of largely forgettable features (e.g., "In the Heat of Passion" 1992). Kudrow landed her first important film role after her small screen success playing a pushy blind date to Albert Brooks in "Mother" (1996). The following year, "Clockwatchers" premiered at the Sundance Film Festival and cast her as a promiscuous aspiring thespian working as an office temp alongside Parker Posey, Alanna Urbach and Toni Collette. Reprising a favorite stage role, she undertook a variation of her TV persona as half of a pair of underachievers who attend a class reunion in the uneven comedy "Romy and Michelle's High School Reunion" (also 1997).

1998 brought Kudrow one of her best role to date as the repressed spinster Lucia (pronounced LOO-sha) in the superb black comedy "The Opposite of Sex". Downplaying her looks by wearing little make-up and unflattering hairstyles and adopting a more reserved tone, she offered a well-rounded portrait of a woman stung by life's disappointments, nearly stealing the film from its superlative cast that included Christina Ricci, Martin Donovan, Lyle Lovett and Ivan Sergei. Continuing her hot streak, Kudrow was tapped to play the wife of psychiatrist (Billy Crystal) treating a mobster (Robert De Niro) in the comedy "Analyze This" (1999), a role she reprised for the 2002 sequel, "Analyze That." Her subsequent film roles in "Hanging Up" and "Lucky Numbers" (both 2000) both were unworthy of her talents and her turn as a woman who suffers a nervous breakdown and becomes convinced she's a dog in "Bark" (2002) did not raise expectations, nor did the long-shelved comedy "Marci X" (2003), a critically reviled film that barely saw the light of day that cast Kudrow as the spoiled daughter of a record industry titan who becomes involved in his ignored hip-hop clients' culture. But as she headed into the final season of her sit-com, Kudrow demonstrated her potent dramatic chops when she appeared in the dizzying but ultimately unsatisfying "Wonderland" (2003), playing Sharon Holmes, the estranged wife of porn legend John Holmes (Val Kilmer), who became embroiled in the real-life 1981 drug murders on Los Angeles' Wonderland Avenue.

As "Friends" wound down to its final episode in 2004, Kudrow was perhaps the cast member best positioned to continue her career on the big screen in roles both comedic and dramatic. To the comedic end, she inked a pact with HBO and teamed with "Sex in the City" writer-producer Michael Patrick King to co-create "The Comeback" (2005 - ), a single camera, 30-minute comedy that cast Kudrow as Valerie Cherish, a neurotic, fading one-time sitcom star desperately hoping to revive her career with a new series while also having her return to primetime documented by a reality TV crew. Kudrow multi-tasked on the show as star, co-writer and producer and provided a knowing glimpse into fragile Hollywood egos, and the series had its admirers, though at times the character's self-centered, desperate bid to reclaim stardom was, however well observed, more painful than funny. On the dramatic--or at least seriocomic--end, she reteamed with writer-director Roos for the ensemble film "Happy Endings" (2005) to tackle a part written specifically for her: Mamie, a tightly controlled woman whose teen dalliance with her step-brother resulted in her giving away her child, only to be confronted by a young wannabe filmmaker who claims to know her son's identity and drawn into a elaborate scheme to obtain the information. Exploring her character's sometimes absurd course of self-discovery, Kudrow delivered another sharply etched performance.