Bile duct stones are routinely removed at time of endoscopic retrograde cholangiopancreatography (ERCP) after biliary sphincterotomy with standard balloon or basket extraction techniques. However, in approximately 10% to 15% of patients, bile duct stones may be difficult to remove due to challenging access to the bile duct (periampullary diverticulum, Billroth II anatomy, Roux-en-Y gastrojejunostomy), large (> 15 mm in diameter) bile duct stones, intrahepatic stones, or impacted stones in the bile duct or cystic duct. The initial approach to the removal of the difficult bile duct stone is to ensure adequate biliary sphincter orifice diameter with extension of biliary sphincterotomy or balloon dilation of the orifice. Mechanical lithotripsy is a readily available adjunct to standard stone extraction techniques and should be available in all ERCP units. If stone extraction fails with these maneuvers, two or more bile duct stents should be inserted, and ursodiol added to aid in duct decompression, stone fragmentation, and stone dissolution. Follow-up ERCP attempts to remove the difficult bile duct stones may be performed locally if expertise is available or alternatively referred to a tertiary center for advanced extracorporeal or intracorporeal fragmentation (mother-baby laser or electrohydraulic lithotripsy) techniques. Nearly all patients with bile duct stones can be treated endoscopically if advanced techniques are utilized. For the rare patient who fails despite these efforts, surgical bile duct exploration, percutaneous approach to the bile duct, or long-term bile duct stenting should be discussed with the patient and family to identify the most appropriate therapeutic option. A thoughtful approach to each patient with difficult bile duct stones and a healthy awareness of the operator/endoscopy unit limitations is necessary to ensure the best patient outcomes. Consultation with a dedicated tertiary ERCP specialty center may be necessary.