Malignant melanoma is an antigenic tumor recognized by specific lymphocytes. Several melanoma-associated antigens have been shown to cause tumor rejection in vitro. Escape from immunosurveillance by melanoma cells is the result of several mechanisms such as total loss or decreased expression of HLA antigens, alterations in the expression of tumor-associated antigens or deficiencies in the antigen-processing machinery. Additional important features include the influence of endogenous and exogenous cytokines such as interferons or interleukins and expression of adhesion molecules or co-stimulatory molecules. All these factor have to be considered for the development of new immunoregulatory treatment modalities against advanced melanoma.