Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that block inhibitors of T-cell activation and function. The use of ICIs can have beneficial effects on more than 14 different cancers, and effects have persisted in some patients for more than 5 years (20%-40%; 5-year survival rate in patients with melanoma)1 (eTable in the Supplement). ICIs block cytotoxic T lymphocyte antigen 4 (CTLA-4; ie, ipilimumab), programmed death 1 (PD-1; ie, nivolumab, pembrolizumab), or programmed death ligand 1 (PD-L1; ie, atezolizumab, avelumab, durvalumab). Given the increasing rate of prescription of ICIs, knowledge of their adverse effects (AEs) is important for physicians in multiple clinical disciplines. This JAMA Insights reviews the clinical presentation and management of the most common and severe ICI toxicities that nononcologists are likely to encounter.