Since the introduction of endoscopic sphincterotomy, stone clearance of the bile duct can be achieved by conventional endoscopic means in up to 90% of patients with stone disease. Several endoscopic therapies for difficult bile duct stones have been introduced. Laser therapy for stone fragmentation under direct visual control via the peroral insertion of a cholangioscope (POCS) in the bile duct has proven to be highly effective, further raising the success rate of endoscopic biliary stone clearance. However, conventional POCS has not gained wide acceptance because of several technical limitations such as fragility, impaired steerability and the need for two endoscopists. These limitations may be overcome with a newly developed single operator peroral cholangioscope, the SpyGlass(®) Direct Visualization System. First clinical data of SpyGlass guided intraductal stone fragmentation with EHL or laser fibers report high safety and efficacy of the procedure.