While advanced melanoma remains one of the most challenging cancers, recent developments in our understanding of the molecular drivers of this disease have uncovered exciting opportunities to guide personalized therapeutic decisions. Genetic analyses of melanoma have uncovered several key molecular pathways that are involved in disease onset and progression, as well as prognosis. These advances now make it possible to create a "Molecular Disease Model" (MDM) for melanoma that classifies individual tumors into molecular subtypes (in contrast to traditional histological subtypes), with proposed treatment guidelines for each subtype including specific assays, drugs, and clinical trials. This paper describes such a Melanoma Molecular Disease Model reflecting the latest scientific, clinical, and technological advances.