Article abstract Although results currently obtained by using standard treatment on patients with advanced melanoma are still poor, more is known about the immunology of melanoma and how melanoma interacts with the immune system than about any other solid tumor. Recent clinical research has focused on two major pathways: the promotion of antigen-specific immune responses and the targeting of specific signalling pathways within the melanoma cells themselves or microenvironmental factors (eg, angiogenesis).This article reviews the relevant research topics about immunology and immunotherapy of melanoma. First, some older immunotherapeutic strategies, such as cytokine therapy with interleukin-2 and tumor-infiltrating lymphocyte (TIL) adoptive immunotherapy, are briefly reviewed in order to place newer treatment approaches in perspective. The newer approaches that are reviewed in detail include immune reconstitution following lymphodepleting chemotherapy, modulation of T-cell regulatory pathways with antibodies to cytotoxic T-lymphocyte antigen 4 (CTLA-4), and recent advances in targeted therapy.