When a new patient is in desperate need of a heart transplant, we are introduced to the life of world-renowned heart transplant surgeon Dr. Alexandra Panttiere. There is nothing conventional about Alex. She is as cutting edge and unorthodox in the OR as she is with the two men in her life. Her approach to medicine is without boundaries, as is her approach to everything else in her world, which is always full of surprises.

When conjoined twins arrive at the hospital with a cancer diagnoses, Alex recommends a very risky surgery, resulting in a major ethical debate within the department. After spending time with the twins and observing their unique relationship, Alex also begins to question her relationship with Pierce.

When a young man is only able to speak sentences backwards, Alex sees this as the perfect opportunity to test out some new technology. While Jesse agrees this is the best course of action, Millicent believes otherwise. This tension within their department might stem from past history which could further complicate things between Alex and Pierce.

Alex and Pierce disagree on whether an experimental treatment for those with advanced stage cancer is right for the hospital's patients. True to form, Alex takes matters into her own hands with a risky move to find volunteers. Meanwhile, Max looks to drastically change the family dynamic with Alex, and Ji-Sung connects with Callahan.

A patient questions Alex's ability to leave personal grief outside the OR when she performs heart surgery on the anniversary of her sister's passing; Millicent dates an artist; Pierce wants to be more of a part of Alex's family.

A case brings back memories for Alex, Jesse and Millicent as they fight to save a heart transplant patient when she sustains devastating injuries in a car crash.

Alex and Ji-Sung fight to save the life of a transgender woman with breast cancer; a consultant from another hospital forces Jesse to confront her feelings for Alex.

When Alex's father needs a new kidney, an unlikely donor emerges and family secrets threaten to destroy the close relationship between father and daughter.

Alex makes her best effort to bring the dying wish of a young heart patient into fruition.

Alex fights to save the lives of Jesse, Pierce and Ji-Sung when a mysterious and deadly illness sends the hospital into lockdown. Meanwhile, Millicent must pick up the pieces when Alex disobeys the orders of the CDC, and an elderly man searching for his missing wife leads Alex to make a drastic decision in her love life.