Tremelimumab is an investigational, fully human IgG monoclonal antibody directed against CTLA-4, a coinhibitory receptor that represses effector T-cell activity in cancer. Tremelimumab has produced promising anticancer responses in early clinical trials. However, a phase III trial of tremelimumab monotherapy versus chemotherapy in advanced melanoma was stopped early when no statistically significant difference in overall survival was observed between the two interventions. This article describes tremelimumab's putative mechanism of action, its preclinical pharmacology and clinical results to date across a range of cancer settings as monotherapy, as well as in combination with other therapies. The failure of the Phase III trial in melanoma is examined and factors affecting the possible future clinical development of tremelimumab are also explored.