A painter's undiagnosed illness affects his work, and House and his team must look at the man's paintings to determine what's wrong with him.

House and the team try to diagnose a man living with severe, chronic pain; Thirteen and Foreman explore their complicated relationship; Cuddy discovers that caring for her baby leaves her with little time to run the hospital.

House and the team take on the case of Nick, a book editor who loses his inhibitions. The team realizes Nick has frontal lobe disinhibition, which causes him to speak his mind having no control over what he says and making him just like House. Meanwhile, House suspects Wilson and Taub are keeping something from him.

The team takes on the case of Valerie, an attractive female executive experiencing random episodes of excruciating pain. House agrees to take the case based on Valerie’s looks, and while treating her, the men on the team are charmed by Valerie’s beauty and personality, with Thirteen looking beyond the superficial to try to discover a link to her illness. Meanwhile, House uncharacteristically attempts to alleviate his conscience by reaching out to a former medical school colleague he wronged.

During a day in the life of Princeton Plainsboro's Dean of Medicine, Dr. Lisa Cuddy, the inner workings of the hospital are seen through her eyes. This day proves to be especially trying as Cuddy wrestles with myriad hospital issues and staff disputes that test her perseverance and skills as an administrator, all while juggling issues in her personal life.