Immune checkpoint inhibitors (ICIs) have transformed the care of cancer patients, providing therapeutic options for advanced malignancies considered otherwise untreatable. However, these agents have been associated with immune-related adverse events (irAEs). ICI-induced diabetes (ICI-DM) is a rare complication of programmed death-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor therapy (~1%) and can be life-threatening, as patients often present with severe hyperglycemia and in diabetic ketoacidosis. We describe two patients with rapid-onset diabetes mellitus associated with anti PD-1 therapy followed by an in-depth review of the literature. We discuss the clinical presentation, potential mechanisms and optimal management of patients with ICI-DM. As ICI use continues to expand across a wide variety of malignancies, clinicians must be aware of this potentially life-threatening irAE to prevent significant morbidity and mortality.