Ipilimumab is a fully humanized monoclonal antibody to cytotoxic T-lymphocyte-associated antigen 4. Data from preclinical and clinical studies have shown that ipilimumab can cause tumor regression in patients with metastatic melanoma with response rates of 5.8-22%. Phase III trials have demonstrated a benefit in median overall survival in the first-line setting in combination with dacarbazine versus dacarbazine alone (11.2 vs 9.1 months) and in the second-line setting in combination with gp100 versus gp100 alone (10.1 vs 6.4 months). The main toxicities of ipilimumab are immune related, most commonly skin and gastrointestinal. Bowel perforation and treatment-related deaths have occurred, although prompt use of steroids and other immunosuppressive agents can minimize this risk.