Melanoma is a malignant melanocytic tumor developing in most cases from epidermal melanocytes. A steady incidence increase (3–7 %) in fair-skinned Caucasian populations in the past four to five decades has utterly transformed the epidemiology and the socioeconomic impact of this formerly infrequent skin malignancy. Early recognition and diagnosis of thinner melanomas has led to stabilization of mortality with improved 5-year survival rates. Phenotype, sun exposure, and genetic predisposition are considered key risk factors. The identification of molecular signatures or mutations based on anatomic location and sun exposure has shed light on the molecular basis of melanoma; 40–50 % of all melanomas are positive for the BRAF mutation. Novel treatments targeting this specific mutation are in clinical use for disseminated disease, e.g., vemurafenib and dabrafenib, which together with novel immunotherapies such as the CTLA-4 blocking autoantibody ipilimumab hold promise to revolutionize the treatment of metastatic melanoma. Surgical excision is the primary treatment of melanoma and of locoregional metastasis and has an increasing role in the treatment of localized metastatic disease.