Autoimmune responses are normally kept in check by immune-tolerance mechanisms, which include regulatory T cells. In recent years, research has focused on the role of a subset of natural killer T (NKT) cells — invariant NKT (iNKT) cells, which are a population of glycolipid-reactive regulatory T cells — in controlling autoimmune responses. Because iNKT cells strongly react with a marine-sponge-derived glycolipid, α-galactosylceramide (α-GalCer), it has been possible to specifically target and track these cells. As I discuss here, although preclinical studies have shown considerable promise for the development of treatment with α-GalCer as a therapeutic modality for autoimmune diseases, several obstacles need to be overcome before moving α-GalCer therapy from the bench to the bedside.