The medical treatment of advanced or metastatic malignant melanoma is still controversial and no standard systemic therapy can be claimed. The selection of patients is an important factor to evaluate the results from clinical trials. Among the chemotherapeutic agents dacarbazine is still the most widely employed drug, because of the scarce evidence of better survival from multidrugs combinations. Fotoemustine is one of the most promising new drugs showing non cross resistance with dacarbazine and effectiveness on brain metastases. Interleukin-2 and interferon are active, but no more than single chemo-therapeutic agents, despite the higher cost. However, ongoing trials are exploring the combination of immuno- and chemotherapeutic agents with some very good preliminary results. In fact, for the above reported reasons, a patient with advanced malignant melanoma should be treated according to research protocols in specialized centers until an effective standard approach will be developed.