Although natural killer T (NKT) cells were discovered over 20 years ago, our understanding of their immunobiology continues to evolve and surprise. NKT cells are T lymphocytes: they arise in the bone marrow, are selected in the thymus, and express a T cell receptor. Unlike classic T cells, however, they are not strictly “adaptive” immune cells: in particular, as a population they express a very narrow range of T cell receptors. The vast majority of mouse NKT cells, for example, express the Vα14-J281 chain and only a finite number of Vβ chains (1). In addition, they express NK cell surface markers, such as NK 1.1. Moreover, unlike classical T cells, they are not restricted by MHC Class I or Class II, but by an MHC-like molecule, CD1d (2). Furthermore, NKT cells do not recognize peptides in the context of CD1d, but rather specialized lipids (3). Functionally NKT cells also reflect major differences from conventional T cells: they are able to produce both classic Th1 (IFN-γ) and Th2 (IL-4) cytokines without prior peripheral stimulation, but when stimulated by their glycolipid antigens downregulate TCR, expand, and divert to a Th1 phenotype (4). Like classical T cells, they are selected in the thymus by a self-molecule: however, it is not a protein, but a trihexosylceramide, iGb3, bound to CD1d (5). Mice deficient in iGb3 demonstrated a severe deficiency of NKT cells, illustrating its critical role in NKT cells selection and survival (5). These features of NKT cells place them into the expanding category of “innate-like” lymphocytes (6). “Innate” immunity has classically been defined by “stereotypical” responses mediated by invariant receptors to defined ligands: for example, the signaling and functional responses of TLR4 when bound to its ligand, LPS. Since the overall TCR repertoire of NKT cells is so limited, the population as a whole responds “innately” to just a few lipid antigens, rather than retaining a population-capability to respond to the full universe of T cell antigens. Finally, and of great interest to the field of hepatic immunity, NKT cells do not circulate freely, but tend to home to and reside for life in specific tissues such as the liver, where they compose ~30% of the intrahepatic lymphoid pool (7).