The appropriate selection of patients for treatment with oral ursodeoxycholic acid (UDCA)—a drug that has virtually no side effects—results in about 50% of patients experiencing safe dissolution of gallstones within 2 years. Eligible patients have small (less than 20 mm in diameter)radiolucent gallstones in a gallbladder visualized by oral cholecystography (OCG); ideal candidates are thin women who have gallstones that are less than 15 mm in diameter, floating when observed by OCG, or of low density on computed tomographic (CT) scanning. Contact dissolution with methyl tert-butyl ether (MTBE) is rapid, effective more often than UDCA, and safe but requires the expertise of an interventional radiologist. Any size and number of cholesterol gallstones that are not CT-dense will be dissolved by MTBE, leaving at most only insoluble debris that is clinically innocuous. Although gallstones recur after dissolution by UDCA or MTBE in 50% of patients within 5 years, recurrent gallstones are usually asymptomatic and/or can probably be dissolved. We conclude that oral or contact dissolution provides an alternative treatment to cholecystectomy for about 30% of patients with symptomatic gallstones.