Gallstone disease is exceptionally common, occurring especially in Western populations, with cholesterol gallstones predominating. Currently, it is believed that one of the essential factors in the pathogenesis of cholesterol gallstones is a physical–chemical event that results primarily from alterations in the lipid composition of gallbladder bile. Cholesterol supersaturation is due principally to excessive secretion of cholesterol into the bile. Several biochemical defects, as well as diet, might cause hypersecretion of cholesterol. The precise effects of diet on cholesterol supersaturation of bile have not been clearly established, although epidemiological, clinical, and animal studies indicate that diet plays an important role in cholesterol gallstone formation. This review summarizes current information on the role of dietary fat in the modulation of cholesterol gallstone formation.