Tina's proposal to use an unorthodox procedure to treat a young man with extreme O.C.D. divides the surgeons at the 311 conference. At the same time, Villanueva must find a way to treat a girl with critical internal bleeding who refuses care because of her religious beliefs. Sung discovers that no good deed goes unpunished when a former patient sues him after her successful surgery creates an unforeseen side effect – abnormally increased sexual appetite.

Hooten's mentor, Dr. Arvin Wayne, walks into the wrong procedure on the wrong day, leading the surgeons at Chelsea General to question the cognitive abilities of one of the hospital's elder statesmen. When a top competitive swimmer suffers a seizure in the emergency room, Villanueva follows his gut – leading to a surprising diagnosis. Tina must perform a risky transvenous thrombolysis with Ty and Michelle's help. And Sydney implies that Lieberman might be a crummy doctor for missing the signs of bacterial endocarditis in a former patient.

When paramedics rush in with a stabbing victim, Villanueva is stunned to realize that the patient is his own son, Nick. Now it's up to Sydney and Hooten to save the young man. With Ty's help, Sung attempts to restore a concert violinist's perfect pitch by removing an astrocytoma that is pressing on the musician's brain. And Buck receives a strange request from the donor in a failed kidney transplant.

Ty and Tina receive a late night call from Afghanistan, where Corpsman Jacob Gold desperately needs help when his fellow Marine suffers a traumatic head injury. Sydney believes a happy infant's unnatural laughter is related to an undiagnosed neurological problem. And Sung and Hooten attempt to reconcile the husband and sister of a brain-dead gay patient, only to find themselves caught in the legal crosshairs of the situation.

During Monday's 311 conference, Hooten calls Dr. Stewart Delany to explain how a careless mistake killed Delany's young patient. But the outcome of the conference leaves the hospital's surgeons conflicted. Sydney and Villanueva operate on Keith Harriman, a young man with extensive injuries from an apparent suicide attempt. Sydney and Buck wonder about the resources wasted on those who cannot or do not want to be saved. And Mark Ridgeway returns, determined to make Ty and Tina pay for their adultery.

Ty and Hooten believe Supreme Court hopeful Judge Beverly Nathenson's facial pain is the result of a brain tumor; upon operating, the surgeons discover a diagnosis much more shocking. Michelle struggles under pressure when a difficult E.R. case proves to be more than she can handle. And Sung and Tina disagree over the course of treatment for an obsessive writer suffering from a rare form of epilepsy.

In the season finale, Hooten and Buck find themselves facing off in court against attorney Mitch Tompkins after a grieving son refuses to comply with his mother's final wishes. Sydney's outrage over the health of a morbidly obese 16-year-old boy further strains her relationship with Lieberman. And a seemingly harmless patient puts one of Chelsea General's own in grave danger.