Natural killer T (NKT) cells are a unique lymphocyte subtype implicated in the regulation of autoimmunity, particularly diabetes and experimental allergic encephalomyelitis in animal models. In some reports, NKT-cell regulation was revealed only following vigorous activation by a synthetic glycolipid, a process that might not occur naturally. Patients with diverse autoimmune diseases have reduced NKT-cell counts and, in diabetes and multiple sclerosis, effective NKT-cell regulation correlates with the secretion of Th2 cytokines. Although current controversy surrounds the importance of NKT cells and their modes of action, they represent a potentially important clinical target.