Antibody-based targeting of the immune suppressor molecule cytotoxic T-lymphocyte antigen 4 (CTLA-4) with ipilimumab has been studied in metastatic melanoma in a number of clinical trials, including a recent phase III trial. This marks the first randomized clinical trial reporting an overall survival benefit using immune modulation in metastatic melanoma. Along with its therapeutic benefits, ipilimumab presents unique challenges to clinicians; these are related to the monitoring of treatment response and the management of drug-related toxicities. This drug is currently being investigated in various cancers, and its indications are likely to be expanded.