Immune checkpoint inhibitors (ICIs) are therapeutic antibodies that target regulatory molecules on T cells and represent the most widely used FDA-approved class of immunotherapy. ICIs are associated with unique immune-mediated toxicities called immune-related adverse events. These toxicities may affect any organ system, and their precise mechanisms of action remain under investigation. Current evidence suggests that activation of T cells is involved, although other components of the immune response have been implicated. This article summarizes toxicities, potential mechanisms of action, management strategies, and other clinical considerations. Unique mechanisms of action and immune-related toxicities of other FDA-approved classes of immunotherapy are reviewed.