The medical therapy of gallstone disease has undergone many changes in the past decade. Two types of dissolution agents have been developed: oral bile acids and contact-dissolving chemicals. In addition, biliary lithotripsy has been used extensively and has been found to be quite successful when used with oral bile acids. The success of these therapies is largely dependent on the type of gallstone being treated. With the success of laparoscopic cholecystectomy, medical therapy of gallstones has become focused on certain patient populations. The strategy in the coming years will be to develop a comprehensive treatment approach for all types of gallstone patients. Most likely, dissolution therapy will be recommended for the elderly or those who cannot undergo cholecystectomy. Small radiolucent gallstones will be particularly amenable to oral bile salt therapy. Larger radiolucent stones, between 5 to 15 mm, will be candidates for biliary lithotripsy. The challenge for medical therapy in the future will be to develop a noninvasive, rapidly acting, oral dissolution agent that will be capable of dissolving cholesterol and noncholesterol portions of gallstones.