As the failure of her chemotherapy sends her in search of a clinical trial that could save her life, Cathy Jamison (Laura Linney) returns to work and lands a job coaching the high school swim team. But just as she begins getting her life back on track and agrees to house a student whose family is moving to Africa, her husband, Paul (Oliver Platt), loses his job and their health insurance.
Meanwhile, Cathy must confront a fellow trial patient's difficult battle with cancer and the baby that her best friend is having with her mentally unstable brother, Sean (John B. Hickey), all while her son, Adam (Gabriel Basso), struggles with his emerging sexuality. And in the wake of a Thanksgiving dinner gone awry, a series of tragic events serves to underscore the harsh realities of the difficult road ahead for Cathy.
Season two guest stars include Alan Alda, Cynthia Nixon, Hugh Dancy and Parker Posey.