Cutaneous melanoma has long been one of the most aggressive forms of cancer, with limited treatment options and a very dismal prognosis. However, in recent years new strategies for treating melanoma have been introduced that significantly improve the outlook for patients with this challenging disease. One of the most important advances has been the development of immunotherapy. The better understanding of the role of the immunological system in tumor control has paved the way for strategies to enhance the immune response against cancer cells. Monoclonal antibodies (mAbs) against the immune checkpoints cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death protein 1 (PD-1) and its ligand (PD-L1) have demonstrated high activity in melanoma and other tumors. This has marked a new era in the treatment of metastatic melanoma and much research is now ongoing with other checkpoint inhibitors and investigating combinations of agents targeting different immune checkpoints.