Unusually for a show that turned out to be a critical and commercial hit, in the weeks before the first episode aired, this show went through several cast and crew changes. The Walker family matriarch, Iva, played by Betty Buckley in the original pilot, was re-cast with Sally Field, and renamed Nora. Walker brother Bryan, played by Jonathan LaPaglia, was re-cast with Matthew Rhys, renamed Kevin, and given a new backstory (instead of Bryan being an ex-husband and father, who was newly out of the closet, Kevin was a never-married lawyer, who was more comfortable with his homosexuality). Marti Noxon was replaced as the showrunner by Greg Berlanti, because of creative differences.
Tom Skerritt and Sally Field have played a married couple before, in Magnolien aus Stahl - Die Stärke der Frauen (1989). They played Julia Roberts' parents.
While the producers were looking for an actor to play the role of Jason McCallister (Robert McCallister's brother and Kevin Walker's love interest), Rob Lowe, who plays Robert McCallister, recommended John Barrowman, who had co-starred with Lowe in "A Few Good Men" on the London stage. The producers offered the role to Barrowman, and he was interested in taking it, but was ultimately unable to work the shooting schedule around the schedule for his own show, Torchwood (2006).
Sally Field and Matthew Rhys are the only actress and actor to appear in every episode of the series.
Balthazar Getty and Sarah Jane Morris departed as series regulars at the end of season three, due to their contracts not being renewed. They made guest appearances in seasons four and five.