Much of the hepatology literature to date has focused on the adaptive, antigen-specific response mediated by classical T-cell populations in both the protection and pathogenesis of liver disease. However, the liver is selectively enriched for cells representative of innate immunity, including natural killer T (NKT) cells. In particular, certain CD1d-reactive T cells are present at much higher frequencies in the liver than in the peripheral blood. Although these cells have previously been defined mostly on the basis of phenotypic markers, recent emerging literature regarding NKT cell populations has revealed considerable functional complexity. This review summarizes the recent literature regarding NKT cells, which may have important roles in a variety of liver diseases. Although there is an abundance of literature on the phenotype, distribution, and function of these cells in mice, much less is known about them in human health or liver diseases. (Hepatology 2004;40:1033-1040.)