Gallstones are found within the main bile duct (MBD) of 7% to 20% of patients undergoing cholecystectomy. MBD stones are the commonest cause of acute cholangitis and acute pancreatitis. Acute cholangitis is the result of infection superimposed on an obstructed biliary system and carries a high mortality rate if left untreated. The mainstay of treatment is a regimen of broad-spectrum intravenous antibiotics followed by prompt decompression of the obstructed biliary tree. Decompression is best accomplished by the endoscopic route, although transhepatic approaches may also be employed. Gallstone pancreatitis may be associated with cholangitis but is also common as a separate entity. Initial treatment is supportive, although new agents designed to suppress the systemic inflammatory response are under development and have proved beneficial in clinical trials. Severe cases should be treated with systemic antibiotics and early removal of the obstructing stones by endoscopic retrograde cholangiopancreatography and endoscopic sphincterotomy. Prophylactic cholecystectomy is recommended to prevent further episodes of gallstone pancreatitis.