Dr. Manning and Dr. Rhodes separately treat complicated cases involving sick babies, only to uncover that the two cases could actually be intertwined. Elsewhere, Dr. Halstead and Dr. Charles treat a homeless man with an upbeat disposition who sheds some valuable insight that prompts one of the doctors to learn a thing or two along the way. Dr. Choi has a Navy corpsman follow him for the day as they deal with the toll of gang violence in the city, while Dr. Reese tries to understand the delicate balance required in her new position.
Dr. Manning and fourth-year medical student 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 where he meets her sibling Denise and uncovers deep-rooted family secrets. Meanwhile, Dr. Rhodes takes on a complicated heart surgery without consulting Dr. Latham and 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..
A car accident that occurs at the Chicago Marathon leaves a victim in critical condition and tests the mettle of Dr. Halstead, April and her fourth-year medical resident brother Noah, who must perform a difficult procedure in the field. A mother brings in her 8-year-old girl experiencing a sudden hearing loss and Dr. Manning is left to tend to the case, which takes a complicated turn. Dr. Choi deals with Olga, a woman who is malnourished, prompting him to bring in Dr. Charles to help assess the case. Meanwhile, Goodwin takes measures to get her personal life in order.
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.
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