The family consists of wife and mother Nora Walker (Sally Field) who must deal with revelations about her husband's infidelity, and her children Sarah (Rachel Griffiths) and Tommy (Balthazar Getty), both married executives at Ojai Foods, Kitty (Calista Flockhart), a conservative activist, Kevin (Matthew Rhys), a gay lawyer, and youngest sibling Justin (Dave Annable), who has recently returned from the Afghan War with a substance abuse problem.

They were joined by Scotty (Luke Macfarlane) – Kevin's boyfriend and later husband – and Nora's brother Saul (Ron Rifkin) and Holly Harper (Patricia Wettig), William's mistress.

His death causes a number of secrets from his life to be revealed—secrets that impact the remainder of his family and which include the introduction of William's mistress Holly Harper and her daughter Rebecca.

Other main storylines throughout the series include the personal, political (usually through Robert and Kitty's and later Kevin's careers) and professional lives of Nora and all the brothers and sisters; their relationships with each other; interaction with Rebecca and her mother (William's mistress) Holly; and the running of the family business Ojai Foods—which is mostly looked after by Saul, Sarah and Tommy along with Holly and Rebecca from season 3 onwards.

After the family sells Ojai Foods, Scotty and Saul open a restaurant and Nora begins working at a radio station which Sarah decides to buy.

After the discovery that she is not, in fact, a Walker, Rebecca must deal with her new place in the family and her new relationship with Justin which could be in trouble with the appearance of Ryan—William's actual secret child.

The season ends with a horrific car crash that leaves Holly severely injured and the fate of Senator Robert McCallister unsure.

Kevin, who has become a low-paid pro-bono lawyer, and Scotty begin the adoption process after their surrogate, Michelle, appears to lose their baby.

[4] Finally, Nora has become distant from her family whilst she searches for a new career and purpose when a unique job opportunity presents itself at a local radio station.

Mark B. Perry (The Wonder Years and One Tree Hill) served as the showrunner for twelve episodes before departing the show in the aftermath of the 2007–2008 Writers Guild of America strike.

Most notably, several of the roles were recast: Robert McCallister was the name of a character on a previous Greg Berlanti production, Jack & Bobby, about a boy who grew up to be the president of the United States.