Active unspecific immunotherapy in an adjuvant or palliative setting has been shown to enhance survival in melanoma patients, and gene therapy now offers new perspectives for active specific immunotherapy. Gene therapy includes the transfer of genetic material performed by either viral or non-viral methods and in vivo or ex vivo. For melanoma the following approaches are suggested: vaccination with tumour-specific, HLA-associated antigens using peptides or 'naked DNA', vaccination with melanoma cells transfected with cytokine genes or B7, adoptive immunotherapy with specific T-lymphocytes or transfected tumour-infiltrating lymphocytes, or transfection of tumour cells with a tumour suppressor gene whose dysfunction plays a crucial role in melanoma.