Rhonda Fernandes is a mother of two with a brain tumor that will be fatal if her surgeons cannot extract it. In a tricky neurosurgery called "wide awake," she will have to talk to her neurosurgeons Guy McKhann and Jeffrey Bruce so that they know they are not damaging crucial motor control areas.

Jon Kuhfeldt married the love of his life. His wife Sherry thought they’d grow old together. She didn’t count on a pernicious liver disease that would bring Jon to his knees and only weeks away from death. His only hope is a liver transplant. His only dream is to walk his daughter down the aisle at her wedding.

John Rankl, a veteran of the Gulf War who is also HIV positive, has been overcoming the odds his entire life. Now, a pump keeps his heart beating and any hope of a future depends on a transplant. But when a donor heart becomes available, there is an accident during the procurement. John has already been put under in the OR. The surgeon goes to tell John's family the news - whether John will be waking up with a new heart or not.

Valeria Simone came to the U.S. as an illegal immigrant crossing the Rio Grande on an inflatable raft. Today she is one of her hospital’s top trauma surgeons. A self-described “hot-blooded Latin,” she flirts with male colleagues, cooks up a Tabasco sauce storm, and rescues colleagues when their patient starts to crash during surgery. In this episode, she treats a man with a bizarre eating disorder that compels him to consume objects made out of metal.

Andree Brown is a professional and single mother who raised her college-age son alone. She has lots of friends, interests and plans until a visit to the doctor reveals cancer in her breast. Viewers are right there with her when she learns whether the disease has spread and what her prognosis might be. It is an acutely intimate portrait of a woman struggling to reclaim her life.

In the ER, Katie Duke, Diana Costine and Marina Dedivanovic return. Katie treats a psychotic patient while Marina cares for an elderly man whose wife of 65 years recounts how the couple first met. It triggers an epiphany for Marina, who decides to break up with her boyfriend Steve while on vacation and reunite with her ex-boyfriend. Diana is shocked when an old friend returns to the ER.