Cholesterol is extremely insoluble in water. As a result, cholesterol secretion into bile is highly regulated and once secreted into bile, solubility is maintained by cholesterol transporters. Understanding the physicochemical relationships between cholesterol and its transporters is key to understanding gallstone formation. Stone formation requires excess cholesterol secretion into bile, which produces cholesterol supersaturation. Many of the epidemiologic risk factors for stone formation such as obesity, femaleness, and age can now be linked to specific abnormalities of cholesterol metabolism. Cholesterol supersaturation is necessary but not sufficient for cholesterol crystal formation. Crystallization also requires a gallbladder motility defect and/or the presence of procrystallizing factors such as mucous glycoprotein or immunoglobulins. The latter seem to be stimulated by gallbladder inflammation. Stone growth is the final step in stone formation and the least well understood. Recent work suggests that cholesterol stones form as agglomerations of cholesterol crystals and that pigmentation is secondary.