Trauma Chief Jorge Villanueva treats what appears to be an attempted suicide by car only to discover that the crash victim suffered a life-threatening brain aneurysm. Renowned neurosurgeon Dr. Ty Wilson is shaken by the case of 11-year-old Quinn McDaniels, whose soccer injury reveals a much graver problem. Workaholic Dr. Sydney Napur solves a case that had the rest of the hospital staff stumped. Meanwhile, Dr. Sung Park performs high-tech deep brain stimulation on a patient with uncontrollable hand tremors.
Sung, Hooten and Villanueva join forces to convince Trisha Miller, a 13-year-old girl with an advanced brain stem glioma, to try surgery one last time before giving up. Shaken from losing a patient, Ty turns to Dr. Tina Ridgeway for support. Meanwhile, Dr. Buck Tierney tries to bully resident Michelle Robideux into pronouncing a potential organ donor brain dead. And Sydney enlists Villanueva's help diagnosing a patient under the care of internist Dr. John Lieberman.
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 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.
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.