A teen patient with abdominal pain firmly refuses any drugs. Meanwhile, Dr. Halstead reconnects with his past when treating a patient; a pregnant woman does everything in her power not to deliver the child; and Dr. Rhodes tries to avoid family issues.

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. 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. 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.

Dr. Rhodes fights to save a mother who's desperate to help her daughter beat cancer. Dr. Charles asks Sarah to conduct his daughter Robin's psych evaluation. When Will and Dr. Manning spend more time together at work, Nina goes to extreme measures to get Will's attention. Meanwhile, Dr. Choi puts pressure on Noah when a residency spot becomes available.

The hospital is forced to evacuate when a toxic chemical is brought into the E.D., leaving patients and the staff in grave danger. Stuck in an elevator, Dr. Charles and Dr. Manning are forced to take drastic measures with a pregnant woman. Goodwin is tasked with making difficult choices and Dr. Rhodes discovers a secret that Dr. Bekker has been holding from him.

Halstead hides the theft of his gun from a suspicious Manning. Tensions are still high between Connor and Bekker, who take a risk operating on an HIV-positive patient. Hank breaks down when he sees a patient from his past.

The hospital goes into lockdown mode when a man with a gun holds medical staff hostage. Goodwin is forced to make a tough decision. Dr. Rhodes begins to realize his time with his father is getting short.

Maggie gets unsettling news about a new friend and breaks protocol to support him. One of the doctors from the Med family is rushed into emergency surgery after a violent assault. A social media influencer lets his users vote on medical advice, forcing Dr. Charles to make a decision.