Melanoma is generally resistant to chemotherapy and radiation therapy. Its unique immunological properties lend support to developing innovative new therapies via manipulation of the patient's own immune system. The use of whole-cell−based tumour vaccines, including autologous, whole-cell allogeneic and cytokine gene-modified vaccines, as well as tumour lysate vaccines, for active specific immunotherapy of melanoma, is discussed in detail with regard to rationale and available clinical data. Although phase II data on the use of melanoma vaccine in the adjuvant setting show promise, there is no randomised phase III trial demonstrating the efficacy of active specific immunotherapy for melanoma. The coming years will bring the results of several pivotal multicentre phase III trials testing the clinical utility of active specific immunotherapy in the management of melanoma.