Ipilimumab is the first drug to show a survival benefit for patients with advanced melanoma and was approved by the US Food and Drug Administration in March of 2011. Ipilimumab enhances antitumor immunity by enhancing T-cell function by blocking the negative regulatory molecule, cytotoxic T-lymphocyte antigen 4 (CTLA-4). Unlike traditional cancer therapy, ipilimumab’s effects may be delayed and occur after initial apparent disease progression. A distinct set of side effects have been described, and ongoing efforts continue to characterize immunologic changes associated with patients who benefit from therapy. Efforts to characterize ipilimumab’s clinical activity in malignancies other than melanoma are ongoing.