In the final season of Cheers, Lilith has an affair with another man and leaves Frasier. The affair later unravels and Lilith returns, seeking reconciliation with Frasier. Although Cheers ended ambiguously with regard to Frasier and Lilith's marriage, at the beginning of the spin-off series Frasier, their divorce had been finalized, with Lilith gaining custody of Frederick and remaining in Boston while Frasier has moved back to his hometown of Seattle. Lilith occasionally appears in Frasier, sometimes with Frederick.
Lilith's first appearance is in the fourth season Cheers episode "Second Time Around" (1986). Lilith's date with Frasier Crane (Kelsey Grammer) does not go well. Lilith disdains Frasier's activities at the bar and the bar itself. Frasier responds to her hostility with some of his own, leading her to walk away. In the fifth season episode "Abnormal Psychology" (1986), Frasier and Lilith are scheduled to appear on a local talk show to debate psychology. Though neither is pleased to see the other, Diane Chambers is convinced that Frasier still has feelings for Lilith and offers to give Lilith a makeover, including untying her hair. This makes Lilith far more attractive to Frasier and during their appearance on the talk show, each sprinkles their psychiatric jargon with double-entendres. Further, Lilith (in full view of television cameras) slides her foot sensually along Frasier's leg. Each is embarrassed by their unprofessional behavior, but at the end of the episode they are swept up again in passion, with Frasier literally carrying Lilith out of the bar for a tryst at Frasier's home.
In "Dinner at Eight-ish" (1987), Frasier and Lilith are living together. They occasionally argue over neatness and other issues, though quickly reconcile. A greater hurdle appears when Lilith finds out about Frasier's past relationship with Diane and becomes angry at what she assumes is deliberate concealment. With the help of Diane and Sam Malone, Frasier and Lilith make up again.
In the sixth-season episode "The Crane Mutiny" (1987), Frasier has misgivings about the growing pressure to propose to Lilith. Bar patrons Norm Peterson and Cliff Claven, for their own amusement, imply that bar manager Rebecca Howe is attracted to Frasier, manipulating her to support the lie. Frasier writes a letter to Lilith to end their relationship and pursues Rebecca, only to quickly learn that she has no idea who he is. He frantically returns home, hoping to destroy the letter before Lilith reads it, but is too late. Lilith angrily confronts Rebecca, believing her to be a romantic rival, and learns the truth. Seeking revenge, she talks Rebecca into feigning interest in Frasier to cause him further embarrassment. Trapped, Frasier proposes to Lilith, having come to realize that she's the only woman for him. Norm and Cliff suggest that this had been their plan all along.
In "Bidding on the Boys" (1987), Lilith is furious at the prenuptial agreement suggested by Frasier. At a "bachelor auction" organized by Rebecca, Lilith bids $2,000 to "buy" Sam Malone as her date. Sam is reluctant to come between Lilith and Frasier, but Lilith begins behaving in a deliberately seductive manner, which Sam finds hard to resist. Frasier jealously interrupts before Sam can succumb and Lilith admits the entire ploy was an attempt to aggravate Frasier. They reconcile with an embrace.
In "How to Win Friends and Electrocute People" (1988), Lilith decides to learn to drive. Sam attempts to give her driving lessons, but quickly learns that she is aggressive and dangerous behind the wheel, showing a recklessness that Sam and eventually Frasier find frightening.
According to an April 1–4, 1993, telephone survey of 1,011 people by the Times Mirror Center for the People and the Press (now Pew Research Center), before the Frasier premiere and the Cheers finale, Sam Malone (Ted Danson) was voted a favorite character by 26 percent, and Frasier Crane and Lilith Sternin were voted favorites by 1 percent each. For a question of spinning off a character, 15 percent voted Sam, 12 percent voted Woody Boyd (Woody Harrelson), 10 percent voted Norm Peterson (George Wendt), and 29 percent voted no spin-offs. Frasier Crane, whose own spin-off Frasier debuted in September 1993, was voted 2 percent to have his own show.
In the opening scene of the 1993 pilot episode of Frasier ("The Good Son"), Frasier is hosting his call-in radio show and relates the following: "Six months ago, I was living in Boston. My wife had left me, which was very painful. Then she came back to me, which was excruciating. ... so I ended the marriage once and for all, packed up my things, and moved back here to my home town of Seattle."
Lilith has child custody of Frederick, and reconnects with Frasier in "The Show Where Lilith Comes Back" (1994). Lilith calls Frasier during his radio show, which surprises him, and mocks Frasier's psychiatric advice to his callers, especially one who overeats and whom Lilith attempts to help. Later at his apartment, Lilith reminds him about their times together during marriage. They make love at one point, but end up regretting it, strongly indicating no chance at a lasting reconciliation. Throughout the series, Lilith reappears on occasion, often rekindling her and Frasier's lingering emotional bond, sometimes over concern about the future of Frederick (Trevor Einhorn), who also made recurring appearances. A running gag through Frasier is that Frasier's father and brother, Martin Crane (John Mahoney) and Niles Crane (David Hyde Pierce), are never pleased to see her. Martin finds her "weird" and usually shouts out in shock when he unexpectedly sees her in his and Frasier's apartment. Niles resents her for mocking the vows at his wedding, but forgives her when she apologizes. Niles and Lilith even have a sexual encounter, which further aggravates her relationship with Frasier, who had thought until then that he and Lilith had a chance at reconnecting. Lilith's presence frightens Martin's dog Eddie, terrifying the normally defiant dog into obedience. Martin's live-in physical therapist, Daphne Moon (Jane Leeves), fancies herself as having minor psychic abilities, and routinely suffers debilitating headaches when Lilith is in town, citing an evil spiritual presence.