Malignant melanoma presents a therapeutic challenge. Patients at high risk for recurrence (stage III) are eligible for adjuvant treatment with IFN-alpha or may enrol in a clinical trial. Both options offer no meaningful survival advantage. Patients with metastatic disease (stage IV) have a 5-year survival of < 10% and have no effective treatment options. Despite aggressive investigations into vaccine therapy, no vaccine has yet received FDA approval. Biological therapies with IFN-alpha and IL-2 have demonstrated a real but minimal effect. Chemotherapeutic options are even more dismal. Single-agent chemotherapy yields a 15-20% response rate of short lived duration. Combination chemotherapy alone or with immunological adjuvants yields response rates of 35-45% but with significant toxicity and no significant improvement in survival. Novel treatment agents that target metabolic pathways, angiogenesis inhibitors, antisense therapies, gene therapies and innovative vaccines may offer hope for an otherwise grave disease.