Season Four has brought many surprises and sadness for the Salinger family. One main storyline surrounding the Salinger's was Charlie's Hodgkin's disease. Charlie discovered that he had this horrible disease early in the season. Throughout season 4, he got treated with chemotherapy. Obviously, this brought a lot of hardship and strains on the family.

After Charlie contracted this disease, the lives of the Salingers changed. Julia and Griffin decided to move home to help take care of Owen and do housework. Also, Griffin sold his bikeshop so they didn't have enough money to stay in their nice apartment. Living at home caused a strain on Griffin and Julia's marriage. They constantly fought and had disagreements. Later, Griffin slept with a girl named Rosalie whom he worked with at the bike shop. Julia became very upset with this news and still has not decided what to do with the marriage.

Bailey decided to help Charlie by taking over his job at the restaurant. He juggled his hours between school and the restaurant. Because he was so busy, he did not have a lot of time to spend with his girlfriend, Annie. Annie, like Bailey, is a recovering alcoholic, so when Bailey was too busy to see her, she began drinking again. Annie, with the help of Sarah, decided to admit herself to rehab. While she was gone, her daughter, Natalie, stayed with Bailey and Sarah in their apartment. Early in Season 4, Bailey and Sarah decided to move in together and share the job as apartment managers. This is how Bailey met Annie. (she lives upstairs).

Claudia has suffered the most out of the Salingers. She has been neglected constantly throughout the season because Charlie has been in the hospital, and Julia and Bailey are too busy running errands to talk to her. Because of this, Claudia went through a rebellious stage where she constantly skipped school. The social workers found out about this and took Claudia and Owen away because they were being neglected. Luckily, Julia and Griffin convinced the social workers to give Claudia and Owen back. More recently, Claudia has a new boyfriend named Jamie (Ross Malinger).

For the past two episodes (after the six week hiatus), Charlie has announced that his chemotherapy worked and that he does not have cancer anymore. This brought complete happiness to the family. Since then, Charlie has found a new girlfriend, Daphne (Jennifer Aspen). Julia and Griffin's marriage is still quite uncomfortable and unresolved. Justin's return from Yale has made Griffin quite jealous because Julia has been spending a lot of time with him. Justin believes that because Griffin was unfaithful to her, she should divorce him. Meanwhile, Annie has returned and Bailey and Annie have returned to being a couple. At first, everything was weird and uncomfortable because they hadn't talked to each other for so long, but Sarah brought them together again.