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Kelsey Grammer as Frasier Crane, a radio psychiatrist. He is fussy, uptight, cultured, and sometimes arrogant. Having grown up with an educated mother and an "average Joe" father, Frasier epitomizes an upper-class sophistication, yet is still sympathetic to working-class culture. After returning to Seattle, he begins embracing his more privileged background and develops a more selfish and aloof manner, possibly due to rekindling his relationship with his younger brother, Niles Crane. Despite his haughty demeanor, however, Frasier has a strong sense of ethics.
Jane Leeves as Daphne Moon (later Crane), an English immigrant from Manchester; a physiotherapist and live-in aide hired by Frasier to help his father. Daphne's eccentric, working-class background and self-professed psychic abilities (which often end up being correct) frequently lead to Daphne's comical non-sequiturs about her unusual family, which is a sharp contrast to the Cranes' incredulity. In spite of their different upbringings, Niles falls for her instantly. Niles's obsession with Daphne and her obliviousness to this is developed throughout the earlier seasons of the series.
David Hyde Pierce as Niles Crane, Frasier's younger brother. He is a psychiatrist in private practice. Educated, coldhearted, and more arrogant than Frasier, Niles's snobby, anxious qualities provide a foil for Frasier's own issues. Despite his aforementioned qualities, he is brave, caring, and well-meaning, which, to his loved ones, more than makes up for his eccentricities and quirks. Niles is very close to his older brother, though their fiercely competitive natures often provide the audience with much humor throughout the series. Like Frasier, Niles has a deep appreciation and respect for the arts, music, and pursuits that are seen as intellectual and prefers these activities over most sports, though he excels in squash and croquet. Niles is severely mysophobic, often given to wiping his hands after human contact, and is even depicted wiping down chairs in public places before sitting on them.
Peri Gilpin as Roz Doyle, the producer of Frasier's radio show. A native of Bloomer, Wisconsin, Roz, one of two single women in the series, is depicted as a sharp contrast to Daphne. Throughout the show, Roz's search for love and liberal approach to dating is the subject of many witty remarks, particularly from Niles. In the middle of series' run, Roz becomes pregnant with her first child, Alice, and the show addresses some of the challenges of being a single mother, including Roz having to borrow money from her boss, and the personal and professional strain that places on their relationship.
John Mahoney as Martin Crane, Frasier and Niles's father, is an outspoken and laid-back Seattle police detective who was forced to retire after sustaining a gunshot wound to his hip. Because this injury renders him incapable of living alone, upon Frasier's return to Seattle, Martin is forced to accept Frasier's invitation to live with him. Though he and his sons share few commonalities, the relationship between the three men strengthens throughout the series. Martin's relationship with his Jack Russell terrier, Eddie, and his pea-green tartan- and twill-upholstered duck tape stricken recliner are a perpetual source of distress for Frasier. He is also known for his fondness for beer (specifically that for Ballantine).
Dan Butler as Bob "Bulldog" Briscoe (main seasons 4–6; recurring season 1; special appearance seasons 2–3; special guest seasons 7–11), a shock jock hosting a sports show that follows Frasier's time slot at KACL.