Psychiatrist Dr. Frasier Crane (Grammer) returns to his hometown of Seattle, Washington, following the break up of his marriage and his life in Boston (which was covered in the series Cheers). His plans for his new life as a bachelor are complicated when he is obliged to take in his father, ex-police officer Martin Crane (Mahoney), who had to retire and is unable to live by himself owing to an injury caused by being shot in the line of duty. Frasier and Martin are joined by Daphne Moon (Leeves), Martin's eccentric, British, live-in physical therapist and caretaker, and Martin's dog Eddie (Moose). A frequent visitor to their apartment is Frasier's younger brother Niles (Pierce), a fellow psychiatrist who, like Frasier, is pompous, snobbish, and overly intellectual. Niles' infatuation with and eventual love for Daphne, feelings which he does not confess to her openly until the final episode of the seventh season, form a complex story arc that span the entire series.
Frasier hosts a popular radio talk show on KACL 780AM (named to honor the show's creators, Angell, Casey, and Lee). His producer is Roz Doyle (Gilpin), a woman with an active romantic life who, while decidedly different from Frasier in taste and temperament, nevertheless becomes a very close friend over the course of the series.