The incidence of metastatic melanoma continues to increase each decade. Although surgical treatment is often curative for localized stage I and stage II disease, the median survival for patients with distant metastases is less than 1 year. The last 2 decades have witnessed a breakthrough in therapeutic options with the development of immune checkpoint inhibitors, small molecule targeted therapy, and oncolytic viral therapy. This article provides an overview of the treatment options available for advanced melanoma, including chemotherapy, targeted therapy, immunotherapy, interleukin-2, and oncolytic viral agents.