Melanomas are the malignant proliferation of melanocytes in skin, mucous membranes, or epithelia of the eye. The incidence of melanoma, and especially cutaneous melanoma, is increasing. Once metastatic there are no curative options. Until recently, chemotherapy with dacarbazine was the best option, even though results were disappointing. New insights into the genetic background of the immune response to tumours have led to the development of targeted therapies that promise a better prognosis. The BRAF inhibitor vemurafenib and the monoclonal anti-CTLA-4 antibody ipilimumab are the first agents to have completed preclinical testing, and further advances are continually being made. The new therapies, however, are accompanied by new side effects, some of which can be life threatening if not recognized in time. This makes it essential that general practitioners know about these potential side effects, and that patients with metastatic melanoma are closely monitored.