Human melanoma represents the fastest growing malignancy in the US. The etiology of melanoma is highly debated as is the role of ultraviolet (UV) radiation in the initiation and progression of melanoma. This article discusses data from UV exposure and its relationship to the development of melanoma from various models of melanoma as well as various genetic alterations seen in oncogenic transformation of melanocytes. Genetic alterations such as the p16(INK4a) deletion, melanocortin 1 receptor (MC1R), RAS, and v-raf murine sarcoma viral oncogene homolog B1 (BRAF) may be indicative of a predisposition to melanoma development. Historical research as well as current data on the significance of the hot spot mutation in BRAF is discussed in its relative potential to the activating mutation in RAS.