Vitiligo is a depigmenting disorder characterized by the development of white patches in various distributions, which are due to the loss of melanocytes from the epidermis. A variety of arguments from clinical observations to research findings in human and animal models support the hypothesis of autoimmunity and are reviewed in this article. The association with autoimmune diseases and organ-specific autoantibodies is well known. Various effective treatment options have an immunosuppressive effect. Today the autoimmune pathogenesis of the disease has become a rapidly evolving field of research. Detection of circulating melanocyte antibodies in human and animal models implicates a possible role of humoral immunity. Histological and immunohistochemical studies in perilesional skin suggest the involvement of cellular immunity in vitiligo. Recently, T-cell analyses in peripheral blood further support this hypothesis. Interestingly, new insights in the association of vitiligo and melanoma may help to clarify the role of autoimmunity in the development of vitiligo.