Natural killer T (NKT) cells are a conserved subpopulation of lymphocytes that recognize glycolipid antigens in a CD1d context. Upon activation through their semi-invariant T cell receptor, these cells rapidly release large amounts of immunomodulating Th1 and Th2 cytokines. NKT cells have therefore been implicated in immune responses controlling various diseases, including infection, cancer, transplantation, and autoimmunity. Stimulation of the immunoregulatory capacity of NKT cells by the prototypical antigen alpha-galactosylceramide results in amelioration of disease in several animal models. This review will focus on the current knowledge of human NKT cells and their role in autoimmune diseases. The features of these cells and their importance in regulation of autoimmunity suggest that NKT cell-based therapies might be an interesting approach for the treatment of autoimmune diseases.