Melanoma is diagnosed in approximately 100,000 patients worldwide and for those with metastatic disease, the 5-year survival is extremely poor at just 6%, because there are no satisfactory treatments. Targeted radionuclide therapy is currently gaining momentum and has evolved into an efficient modality for the treatment of patients with malignancies such as non-Hodgkins lymphoma in whom standard antineoplastic therapies are not effective. Melanoma is named after the pigment melanin, which in turn is derived from the Greek word for black. Most melanomas are pigmented by the presence of melanin, some of which is extracellular as a result of cellular turnover. Thus, melanin presents a promising target for the drugs carrying a cytotoxic payload of radiation provided such therapies spare other melanotic tissues. There are a variety of substances that could potentially serve as delivery vehicles of radionuclides for the treatment of melanoma. These substances can be divided into melanin binders, melanin precursors and binders to melanogenesis-related proteins. The authors are optimistic that therapeutic agents targeting melanin to deliver radionuclide therapy could appear in the clinic within a decade.