Niles Crane, like Frasier, is also a psychiatrist. He runs his own practice in Seattle, Washington and often makes fun of Frasier's profession as a radio psychiatrist. Even so, the two are very similar: snobby with distinct tastes. He likes fine art and fine wine. Much has been commented on the show about how Frasier and Niles are best friends, even comparing them to the Collyer brothers.

For years, the main gag on the show was Niles' feelings for Martin's physical therapist, Daphne Moon. Because of his shyness, Niles never expressed his love for Daphne, resulting in humerous situations.

Niles has been married three times on the show. His first wife was Maris. Maris was never shown on the show, so all the audience got was descriptions of an uptight, physically weak, thin, WASPish woman. His second wife was Mel Karnofsky in 1999. This marriage was short lived when Niles professed his love for Daphne. Both Maris and Mel tortured Niles with long, drawn-out divorces. Mel's divorce stipulated he must pretend to be married to her so that their high society friends wouldn't find out, and that he musn't be seen with Daphne in public. Eventually they got divorced and Niles married Daphne Moon. The two are expecting a baby which will probably be born this year, as 2004 is the final year for the show.