Melanoma is one of the most aggressive human cancers. Its cells are inevitably resistant to conventional therapies. In recent years, better understanding of melanoma biology, has led to the development of a number of new potential therapeutic agents. Many of these compounds are being tested in early phase of clinical trials, some have already reach phase III. In August 2011 the FDA approved a new drug - Wemurafenib (PLX4032) to treatment unresectable and/or metastatic melanoma. The current article is an overview of the major proteins, signaling pathways and networks involved in the development and progression of melanoma, with particular emphasis on elements that are the most promising targets for anticancer therapy.