Hormonally active vitamin D3, 1,25-(OH)2D3, is believed to have a role in the prevention of cancer formation and in limiting the aggressiveness of cancers that do arise. Therefore,much interest is presently being focused on 1,25-(OH)2D3 and its analogues as potential treatments for various cancers including melanoma. This article discusses the evidence in favour of a role for 1,25-(OH)2D3 in protection against the progression of melanocytic lesions and also summarizes the mechanisms by which 1,25-(OH)2D3 may act to protect against melanoma development and progression.