The past decade has witnessed impressive new developments for the treatment of melanoma. The discovery of key oncogenic driver mutations, upon which tumor establishment and progression are dependent, changed the prognosis of patients with stage IV disease. Extensive preclinical and clinical studies have shown high response rates and survival benefits over conventional chemotherapies provided by target-specific inhibitors of BRAF- or NRAS-activating mutations. Recent genomic analyses of melanoma have also given new potentially targetable driver mutations. In addition, the quickened pace of development of immune checkpoint inhibitors for the treatment of melanoma offers the unique opportunity to provide a long-term clinical benefit. In this emerging era, predictive biomarkers for the selection of patients are required to help us develop an optimal therapeutic strategy.