Failure of cholesterol homeostasis in the body can lead to cholesterol gallstone disease, the most common and costly gastrointestinal disease. The primum movens in cholesterol gallstone formation is the hypersecretion of hepatic cholesterol; this condition leads to bile chronically supersaturated with cholesterol which is prone to rapid precipitation as cholesterol crystals in the gallbladder. Essential topics reviewed here deal with pathways of biliary lipid secretion, cholesterol solubilization and crystallization in bile, according to recent advances. Main in vivo events in cholesterol gallstone disease are also described.