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.

Dr. Manning's actions with a recent patient lead to serious repercussions. April and Noah disagree over a patient who is injured after a beating. Dr. Charles is visited by a childhood friend with a surprising revelation.

The crossover starts on Chicago Fire S08E04 Infection (I). It continues on Chicago PD S07E04 Infection, Part III (III).