No effective therapy for metastatic melanoma exists. Polychemotherapy or chemoimmunotherapy have not shown survival benefits. Vaccines have shown little activity in stage IV disease. To advance the identification of effective agents, new drugs can and should be offered as first-line treatment. Efforts must be made to improve understanding of the biology of malignant melanoma. Too many phase III trials have been conducted with a poor understanding of the mechanism of action of the involved drugs.