The development of immune checkpoint inhibitors (ICI) has dramatically changed the clinical management of metastatic melanoma and other solid tumors. Despite exclusion from initial clinical trials, there is a growing body of retrospective data that suggest ICI can be used in patients with underlying autoimmune disease (AID) with a tolerable level of anticipated immune-related adverse events (irAEs) and a rate of severe irAEs comparable to that of patients without underlying AID. Coordination with other subspecialists and careful monitoring for irAEs is critical in safely managing these patients. Studies exploring novel approaches examining the use of targeted immunosuppressants in the prevention and management of irAEs, as well as multiple studies currently underway are aimed at establishing safe clinical practices when using ICI in patients with underlying AID.