Gallstones are a common problem in the general population, and have an even higher prevalence in the obese and in those losing weight. Complications of gallstones include biliary colic, acute and chronic cholecystitis, and pancreatitis. Three conditions are necessary for cholesterol gallstone formation: supersaturation of bile with cholesterol, nucleation of cholesterol crystals, and gallbladder stasis. In obese subjects, these pathogenetic mechanisms may be modiﬁed, leading to a predisposition to gallstone formation. This chapter will review the pathogenesis of cholesterol gallstones, and the eﬀects of obesity and weight loss on gallbladder disease.