This decade has introduced drastic changes in melanoma therapy, predominantly due to the materialization of the long promise of immunotherapy. Cytotoxic T cells are the chief component of the immune system, which are targeted by different strategies aimed to increase their capacity against melanoma cells. To this end, reprogramming of T cells occurs by T cell centered manipulation, targeting the immunosuppressive tumor microenvironment or altering the whole patient. These are enabled by delivery of small molecules, functional monoclonal antibodies, different subunit vaccines, as well as living lymphocytes, native or genetically engineered. Current FDA-approved therapies are focused on direct T cell manipulation, such as immune checkpoint inhibitors blocking CTLA-4 and/or PD-1, which paves the way for an effective immunotherapy backbone available for combination with other modalities. Here we review the biology and clinical developments that enable melanoma immunotherapy today and in the future.