Invariant NK T (iNKT) cells are a subset of T lymphocytes that recognize glycolipid antigens bound with the antigen-presenting molecule CD1d. iNKT cells have potent immunoregulatory activities that can promote or suppress immune responses during different pathological conditions. These immunoregulatory properties can be harnessed for therapeutic purposes with cognate glycolipid antigens, such as the marine sponge-derived glycosphingolipid α-galactosylceramide. Preclinical studies have shown substantial promise for iNKT cell-based treatments of infections, cancer and autoimmune and inflammatory diseases. Translation of these preclinical studies to the clinic, while faced with some obstacles, has already had some initial success. In this article, we review the immunodulatory activities of iNKT cells and the potential for developing iNKT cell-based prophylactic and curative therapies of human disease.