Among the stage veterans scheduled to appear on the show is Martin Short who will play an eccentric attorney in at least 3 episodes. In addition, Aidan Quinn will play a charismatic investment firm CEO in at least 4 episodes, Jennifer Jason Leigh will return to the series for 4 episodes, reprising her performance as Jill Price-Grey, and Pablo Schreiber will guest star, playing an army supply sergeant, with ties to the show's lead character. Other guest stars will include Lindsay Sloane, David Clennon, Olga Sosnovska, and Gary Anthony Williams.

Weeds centers on Nancy Botwin (played by Mary Louise Parker), a former suburban mom-turned-pot dealer. In the new season, she has moved to New York and is completing probation in a strictly monitored halfway house. The series also features Justin Kirk, Hunter Parrish, Alexander Gould, and Kevin Nealon.