Management of patients with metastatic melanoma has been revolutionized over the last few years with targeted anti-BRAF therapies for BRAF-mutant melanomas (in about 50% of the cases) and immunotherapy with anti-CTLA-4. Several new drugs are now authorized and available. Because of their new mechanisms of action, they also have new adverse events and guidelines concerning their safety are of critical importance. New innovative strategies using combination of targeted therapies and immunotherapies with anti-PD-1 are in accelerated development. The quality of patient-physician relationship is central to this promising but complex new paradigm of treatment.