Despite a major effort in clinical research scrutinizing various treatment regimens for patients suffering from metastatic melanoma the prognosis for these patients still remains poor. The treatment options tested have ranged from monochemotherapy, polychemotherapeutic approaches including highly toxic regimens requiring autologous bone marrow rescue, immuno-modulatory therapies, e.g. defined cytokines such as interferon-alpha and interleukin-2 as well as vaccination therapy with dendritic cells or genetically modified tumour cells, and bio-chemotherapy. Although immuno-modulatory approaches are currently regarded as the most promising, to date no improved overall survival has been achieved by any of these measures especially if tested in large multicentre trials. The focus of this review will be on classical chemotherapy with emphasis on both cutaneous and uveal melanoma.