Metastatic melanoma treatment has been a source of incredible amount of clinical and basic research information. The widespread presence of BRAF mutations suggested the possible role for BRAF inhibitors as treatment. Once used in patients, results were beyond anybody expectations. But the presence of cutaneous side effects and the relatively short lived responses to BRAF inhibitors triggered more research in this MAPK pathway. Better understanding of the pathway led to the introduction of MEK inhibitors. The combination controlled side effects and improved prognosis in these patients. Now, immunotherapies have open a new space with greater efficacy and new cutaneous side effects. Vitiligo-like lesions and lichenoid reactions are immune-mediated adverse events that are opening new areas of clinical and translational research.