Immune checkpoint inhibitors (ICI) are a major class of cancer therapeutics that may cause durable responses in a growing proportion of patients with metastatic cancer. These agents remove negative regulators on T cells and may cause autoimmunelike toxicities that affect all organ systems. Monoclonal antibodies are much less commonly associated with traditional hypersensitivity reactions. Herein, we discuss the pathophysiology, clinical presentation, and management of toxicities of ICI and discuss their broader context within drug hypersensitivity.