Immune checkpoint inhibitors have revolutionized treatment and overall survival for several different types of cancer. Antibodies to cytotoxic T-lymphocyte-associated protein 4 and to programmed cell death protein 1 and its ligand enhance cytotoxic T-cell survival, thus augmenting antitumor action and consequently inducing immune-related adverse events, of which the most relevant is diarrhea and colitis. This review compiles recent data on pathophysiology, clinical manifestations, and treatment of immune-mediated colitis (IMC). The pathogenesis of IMC is not completely understood, but recent studies have focused on the role of regulatory T cells and interactions with the gut microbiome. While sharing similarities with inflammatory bowel disease, IMC is considered a distinct form of colitis with acute onset and rapid progression leading to potential complications including bowel perforation and death. Prompt recognition and management of IMC is imperative for optimal outcomes. Although prospective clinical trials are lacking to guide therapy, recent guidelines recommend early endoscopic evaluation to establish the diagnosis and prompt initiation of corticosteroids. Response to first-line therapy should be assessed early to determine the need of escalation to biologic agents. With treatment, most patients will experience full resolution of symptoms, and subsequent rechallenge with anti–programmed cell death protein 1 or anti–programmed death-ligand 1 inhibitors can be considered.