Melanoma is the most lethal form of skin cancer and its incidence is rapidly rising. Breakthroughs in the understanding of the basic biology of melanoma in the past decade have yielded several new treatments, and advances continue to be made on a variety of fronts. One such area involves the delineation of changes in mitochondria that occur during melanoma formation, and how these changes affect responses to therapy. In this review, we summarize recent developments on the multiple functions that mitochondria play in melanoma, and how these roles are currently being evaluated as new targets for clinical intervention.