Dr. Rhodes begins a fellowship in cardiothoracic surgery, only to have problems with his new boss. Dr. Choi is the new chief resident. Dr. Charles approaches Sarah with an interesting opportunity that catches her off-guard. April faces her recently discovered illness.

Dr. Manning and Jeff Clarke are forced to figure out a mystery illness when an Indonesian man who doesn't speak English arrives at the hospital in dire straights. Maggie takes Dr. Halstead to her family reunion. Dr. Rhodes takes on a complicated heart surgery without consulting Dr. Latham. Dr. Reese and Dr. Charles encounter a woman experiencing an unusual pregnancy.

Several patients are discovered to have the same rare infection, prompting Dr. Charles' daughter Robyn, an epidemiologist, to be brought in to find the common link. Dr. Choi and Dr. Rhodes work on an elderly man who is discovered to be very ill, but a conflict in how to best treat him develops between his son and his young girlfriend. Meanwhile, Dr. Reese tries to help a young drug addict and Maggie tends to a patient who is dear to her heart.

Dr. Manning tends to a young cancer patient and struggles to inform the parents of her dire condition. Elsewhere, Dr. Reese gets contacted by Danny, the troubled young man, and turns to Dr. Charles and Det. Lindsay for help in resolving a difficult situation. Goodwin and Maggie do their best to clear the logjam in the hospital and Dr. Rhodes fine-tunes his instincts after both Dr. Latham and Dr. Halstead pick up on things he doesn't. Meanwhile, a teenage science geek and her friends impress Dr. Choi and Natalie with their bio-engineering lab.

Dr. Halstead and Dr. Manning deal with two warring brothers who are brought together when one finds himself in desperate need of a kidney. Dr. Reese's former patient Danny comes to a crossroad. Dr. Rhodes and Dr. Latham treat a 16-year-old girl with a genetic condition in need of surgery, but whose overprotective mother disagrees with that course of action. A convict with unusual intentions puts himself in the hospital and Dr. Charles meddles in his daughter Robyn's personal life, much to her dismay. Meanwhile, Dr. Halstead and April make a discovery that complicates her treatment for TB.

Dr. Rhodes and Dr. Charles' heart transplant patient gets into a car crash, revealing issues that could complicate her surgery. A past arrest causes trouble for Maggie when the arresting officer is brought to Chicago Med with a serious injury. Elsewhere, Dr. Manning and Dr. Halstead must defend their actions when explaining a patient's cause of death. Meanwhile, Dr. Halstead attempts to treat an uncooperative horse jockey.

It's a long night on the graveyard shift at Chicago Med, especially for Dr. Reese, who must deal with pronouncing patients dead on more than one occasion. April gets called in to work, much to the dismay of Tate, who pressures her to slow down. Meanwhile, Dr. Charles passes along some vital news to Dr. Latham, and Goodwin asks Dr. Rhodes to work on a most unusual patient.

Dr. Manning and Dr. Charles treat a teenage girl with a rapidly changing set of symptoms that has everyone perplexed. Dr. Choi and medical student Jeff Clark encounter a 19 year-old tough guy who is brought into the hospital in severe distress. Once they establish the cause of the pain, the situation quickly turns dangerous and a resolved Dr. Reese does her best to help. Dr. Halstead must deal with a difficult case that is further complicated by Dr. Stohl, who has a camera crew following him around to shoot a promotional video spotlighting the hospital.

Dr. Rhodes convinces Dr. Latham to join him for a medical trip out of town. Dr. Manning treats an 8 year-old cancer patient who wants to give up on his battle. Elsewhere, an unhealthy woman with heart problems is brought in and doesn't want to listen to doctors. Meanwhile, Dr. Choi, Dr. Charles and Dr. Reese work on a complicated case involving a woman with a personality disorder.

Chicago Med braces for an influx of trauma patients when a pre-dawn pileup finds the hospital in full scramble mode. As a result of the storm and emergencies, supplies become limited and Goodwin, Dr. Manning and Dr. Halstead must deal with making an impossible decision. Meanwhile, Dr. Choi handles a severely burned patient who has one final request and Dr. Charles deals with an agitated patient.

Dr. Reese is contacted for help by a troubled teen in a psychiatric facility and Dr. Manning tries to help parents make a decision about their comatose daughter's surprise pregnancy. April begins to deal with repercussions from her personal life. Meanwhile, Dr. Choi and Dr. Rhodes work to save both a young girl from Ecuador who collapsed mid-flight, as well as her mother, who made great sacrifices for her daughter.

A hacker demanding a ransom payment shuts down the hospital computer system, forcing the doctors to diagnose patients without the aid of technology. A stressed Goodwin struggles to keep the hospital afloat when an unexpected visit from her ex-husband Bert and his new girlfriend make matters worse. Making use of his former navy experience, Dr. Choi and Noah have to locate a bullet inside a patient with a gunshot wound. Meanwhile, Sarah feels Dr. Charles may be trying to push her out and Robin's unusual behavior worries Dr. Rhodes.

A new hotshot doctor arrives at Chicago Med causing competition for Dr. Rhodes, Dr. Halstead and Dr. Manning work together to diagnose a Syrian refugee without a medical record. When Robin is admitted back into the hospital for more complications, Dr. Reese takes a different approach to her treatment. Distracted from work because of Robin's worsening case, Dr. Charles is challenged by Goodwin and Noah hosts a graduation party that brings everyone together.

The doctors of Chicago Med take their opinions to the extreme as they try to bring justice to the perpetrator in the shooting of Dr. Charles. Dr. Halstead and Dr. Manning work on a heart-wrenching case that forces them to examine their own matters of the heart. Though Robin’s brain tumor was removed and she is discharged from the rehabilitation center, Dr. Rhodes remains on edge that her problems are not quite resolved. Meanwhile, Rhodes gets blindsided by his colleague Dr. Bekkar, Maggie sticks up for a patient and Dr. Choi and April try to navigate their new working relationship.

Bekker takes drastic action to keep Rhodes from leaving Med for good. Meanwhile, Halstead questions Manning's feelings about their upcoming wedding, Ethan receives shocking news about his sister, and Dr. Charles mourns a loss.

The team deals with the aftermath of a school bus crash. Dr. Charles worries Dr. Halstead is putting his medical license in jeopardy. Maggie helps a friend in need.

Carol receives a second chance at life when a new heart becomes available. Ethan and Dean find themselves in hot water with an old patient. Will faces the consequences of the stolen trial medication.