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Season 1

The fictional affluent Los Angeles, California suburb of Agrestic (an English word meaning "characteristic of the fields or country", but having a second meaning as "crude: lacking the qualities associated with sophistication") is home to Nancy Botwin (Mary-Louise Parker), whose husband Judah (Jeffrey Dean Morgan) has recently, and suddenly, died. Nancy begins dealing marijuana to locals in her suburban town in order to support her household while maintaining an upper-middle-class lifestyle. As depicted in the series, Agrestic has a public school system, where Nancy's children Silas (Hunter Parrish) and Shane (Alexander Gould) both attend. Botwin befriends the manic, image-obsessed Celia Hodes (Elizabeth Perkins) president of the Agrestic PTA, who has several domestic issues. Heylia James (Tonye Patano), assisted by her nephew Conrad (Romany Malco), supplies Nancy with marijuana. Andy Botwin (Justin Kirk), brother of Nancy's late husband, and the family's black sheep, says he has moved into the Botwin household to help Nancy out, but perhaps he is just there to free-load.

Season 2

The second season, while still comedic, takes a darker turn as Nancy gets deeper into dangerous activity. She begins to grow her own plants against Heylia's advice, but with the assistance of Conrad. Several other Agrestic residents help Nancy also, including her brother-in-law, Andy, and the Town Councilman, Doug Wilson (Kevin Nealon). Meanwhile, she also has a dangerous relationship with a DEA agent named Peter Scottson which ends badly, especially for him. Nancy's sons become increasingly more aware of her drug dealings, and each forms his own way of dealing with that information. Having recovered from breast cancer, Celia defeats Doug in an election. Unaware of her friends' activities, Celia tries to turn all of Agrestic into a drug-free zone, and finds herself in unexpected circumstances. Andy, concerned about the possibility of being sent to Iraq due to a long-forgotten Army Reserve commitment, decides to take up religion, after a fashion. The season concludes with a cliffhanger, with several characters posed in a Mexican standoff.