Malignant melanoma is one of the most common cancer types among the Caucasian population. While the prognosis is excellent for patients diagnosed at an early stage and treated by adequate surgery, unresectable or advanced metastatic diseases shrink the overall survival at 5 years dramatically to less than 10%. For disseminated malignant melanoma, the appropriate systemic medical treatment is still controversial. Fortunately, progress in the molecular biology and in the understanding of pathogenesis has been made recently and should in the near future translate into molecular-based therapeutic strategies. In this review, we briefly describe the status of current treatment strategies and existing standards for malignant melanoma. We will focus on the new and emerging compounds including recent developments of targeted therapy such as antiangiogenic and immunomodulatory drugs, Bcl-2 antisense therapy, raf kinase inhibitors, heat shock protein modulators, anti-cytotoxic T lymphocyte-associated antigen (CTLA)-4 monoclonal antibody and finally PARP and proteasome inhibitors.