The prognosis of stage IV metastatic melanoma is poor. An overall 1-year survival of 25.5% and a median survival of 6.2 months were reported without any significant improvement during the last 30 years before the introduction of new drugs (immune checkpoint inhibitors and targeted therapies) which completely modified the therapeutic approach and induced an overwhelming improvement on the survival rates of these patients. This review will analyze the therapeutic tools available for the treatment of patients with metastatic melanoma, including adjuvant interferon and locoregional therapies (surgery, radiotherapy and electrochemotherapy) and will mainly focus on the presentation of results obtained by the new treatments (checkpoint inhibitors and targeted therapies).