Obesity is associated with increased bile stasis and cholesterol saturation, and an increased risk of gallstone development. Conversely, bile composition is normalized following reduction in body weight. It would appear advantageous to promote weight loss in obesity, which would reduce the predisposition to gallstone formation. Despite the potential health benefits of weight reduction, very-low-calorie diets appear to increase the risk for cholesterol crystal and gallstone formation. The incidence of gallstone formation seems to be dependent on the degree of caloric restriction, the rate of weight loss, and the duration of the dietary intervention. Thus, faster rates of weight loss for longer periods of time are associated with increased risk. Available data obtained from prospective studies of subjects during active weight loss suggest that newly formed gallstones occur within 4 weeks and with incidence rates 15 to 25-fold higher than in the general obese population. The stones produce symptoms in approximately one-third of the subjects, of whom approximately one-half will undergo surgery. Proposed mechanisms underlying gallstone formation during weight reduction include bile stasis due to reduced caloric intake, increased biliary cholesterol saturation secondary to increased cholesterol mobilization, and increased nucleation due to changes in bile arachidonate and glycoprotein concentrations. Data are lacking on the effects of gradual rates of weight loss and risk of gallstone formation.