Dr. Murphy treats a patient who has an illness that is not only unpredictable in nature, but also unlike anything he or the team has seen before. Dr. Claire Brown continues to work through her grief, still reeling from Dr. Neil Melendez's death.

Shaun has a hard time balancing his fears and concerns about potentially jeopardizing Lea's health and wanting to be with the woman he loves. Claire looks for a way to grieve Melendez's death. Park and Mia discuss their future together.

When someone mistakenly brings a hallucinogen-laced dish to the hospital's company potluck, much of the hospital staff and doctors are incapacitated -- leaving doctors Murphy, Glassman and Allen forced to take on all the hospital's cases, further exacerbating Dr. Murphy and Dr. Glassman's conflicting work styles.

Shaun and Lea’s long-awaited wedding reception is interrupted by a violent attack at the hospital and the entire team must mobilize to save the victims. Meanwhile, the trauma of seeing people he cares for in life-threatening situations is affecting Shaun in more ways than one.

In the midst of a heatwave, Dr. Shaun Murphy and Dr. Danica Powell are at odds when it comes to their patient’s surgery. Their heated stalemate tests Shaun’s patience and his willingness to compromise. Meanwhile, when the hospital loses power, Lea and Dr. Aaron Glassman are forced to come up with a quick solution or risk a total shutdown that could risk patients’ lives on the 100th episode.

Shaun and Lea struggle to balance their parental duties with their personal lives. Meanwhile, Park and Morgan try to find the time and space to reignite their romance amidst the demands of parenthood and work, and Lim's mother makes a surprise visit.

The team must deal with a mass casualty event that forces them to put aside their emotions following a recent tragedy.