Gallstone disease is common and costly, creating over 700,000 cholecystectomies annually. Its complications consume approximately $6.5 billion in the United States. Surveys using noninvasive ultrasonography have identified its true prevalence and the associated risk factors. In developed countries, at least 10% of white adults harbor cholesterol gallstones; women have twice the risk, and age further increases the prevalence in both sexes. Gallstones reach epidemic proportions in the North and South American Indian populations, accompanied by an increased risk for gallbladder cancer. In contrast, the rate in sub-Saharan Africa and Asia is quite low. Obesity, a major risk factor, likely relates to insulin resistance (the metabolic syndrome). Evolution and circumstance in American Indians may have ironically selected those with "thrifty" genes that conserve energy. Our abundant access to food places us at the increased risk of obesity and cholelithiasis. The general rise in obesity in many countries raises the specter of heightened disease, best identified by epidemiologic studies.