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The contemporaneous treatment of cutaneous metastatic melanoma (CMM) has been revolutionized in a process started decades ago with the better understanding of cancer genetics, cancer biology and the functioning mechanisms of the immune system, which were more recently translated from basic and clinical research into efficacious and effective new drugs. At the turn of the 21^st century, patients with CMM had very few treatment options and their survival was measured in few months. Traditional chemotherapy or cytotoxic drugs had very limited non curative potential, with OS in the ranging from 6 to 12 months, at best.

Currently, the use of immune check point inhibitors (ICIs) and drugs directed at blocking mutated BRAF gene proteins as well as MEK inhibitors have transformed the landscape of CMM treatment, with immense positive impact on hard surrogates such as overall survival (OS) and disease-free survival (DFS) and on the quality of life (QoL) of such patients.

Our objective here is to review the last ten years of data regarding this evolution, as well as acknowledging its pitfalls and limitations, while trying to look forward in the search for biomarkers that could better tail treatment choices while preventing unnecessary toxicities.