Cathy finds that her experience with the great Dr. Atticus Sherman isn't anything like she thought it would be. In addition to not appreciating his bedside manner, not believing that he pays any attention to her file, or not believing that he sees her anything more than another nameless face in his office, Cathy learns he is conducting a clinical trial, about which she learns from another of his stage 4 patients, an extremely positive woman named Nadine, in which he has no space for her. Meanwhile, Cathy and Sean's relationship is still strained over the fact that she kept her illness a secret from him for so long. As such, he is functioning even less well than normal, which means that Cathy is replacing him in many of Rebecca's "baby partner" functions. Rebecca makes an unusual request of Cathy, and further tells Cathy of a decision that doesn't sit well with her. And Cathy's return to work, where everyone now knows of her illness, places both her and Adam in an uncomfortable position.

In her day life, Cathy runs into Dr. Sherman and his much younger second wife, Gia, who invites Cathy and Paul over for dinner. Not wanting to offend the person who is potentially saving her life, Cathy accepts. From dinner, Cathy learns a little bit about how to live in the face of death. It is difficult for Cathy to watch Lee give up on life as he decides to drop out of this trial, the latest failure of many in terms of trials. Based on what Cathy finds hidden in her kitchen, she tries to convince Lee to fight for his life. Cathy and Adam lead a campaign to find a missing Sean, who they are more concerned about now that winter has arrived. Adam learns the God that is Sean among the homeless. Based on Paul's assertion that Mykail is losing his freedom because of his obsession with Andrea, Mykail decides on his future. And one of Mykail and Paul's "under the counter" customers pays them in something besides cash, which adds some spice to stodgy Paul's life.

Cathy, Paul and Adam are getting ready to head to Italy for the Christmas holidays using Paul's cut from the electronics store thefts. They still haven't found Sean, but they feel they need to focus on themselves as a family. They are also leaving behind Andrea who is in engaged bliss to Mykail, with who she will spend the holidays. Owen tells Paul about the imbalance in store inventory, which leads to a revelation from Mykail which could affect his relationship with Andrea. Adam spends time with Poppy before he leaves. But he also finds out some information about Poppy's reality, which ultimately makes him understand why she acts the way she does. And Dr. Sherman asks Cathy to be "show and tell" to one of his classes. She tries to make her reality and the students' reality a little closer together. And just before the Jamisons are ready to head to the airport, Cathy receives a telephone call from Lee, who has an important pre-Christmas request from her.

With Paul (Oliver Platt) recovering from his near-fatal heart attack, and Andrea (Gabourey Sidibe) returning from her African adventure, Cathy (Laura Linney) creates an alter ego as she gets some good news about her chemotherapy trial.

Cathy plans a birthday party.

Cathy inadvertently inspires Andrea to get her sparkle back.