Over the last decade, both immunotherapy and gene therapy have emerged as exciting new modalities in the treatment of malignant melanoma. The fact that many melanoma patients mount cellular and humoral responses against their tumors, and that melanomas express both HLA antigens and tumor-associated antigens (TAA), has led to an increased interest in the treatment of melanoma by manipulation of the immune system. Advances have occurred in several areas, including a) the use of monoclonal antibodies, alone or in combination with cytokines, b) tumor vaccines, using whole cell preparations or cloned melanoma antigens, c) adoptive immunotherapy, with tumor-infiltrating lymphocytes (TILs) and cytotoxic T lymphocytes (CTLs), and d) gene therapy, designed to increase the immunogenicity of the tumor, increase the effectiveness of the TILs, or alter the basic mechanisms of tumor cell growth and regulation. Some of the advances in these areas are discussed.