Cholangioscopy is gaining renewed interest and gradually expanded use as a result of recent technical improvements in endoscopes and accessories, coupled with shortcomings in the accuracy of currently available techniques for biliary sampling and diagnosis. Challenging clinical dilemmas that may benefit from its application include early diagnosis of cholangiocarcinoma in the setting of primary sclerosing cholangitis, early identification of biliary infection or ischemia following orthotopic liver transplantation, and selective duct access with wires and other devices during therapeutic endoscopic retrograde cholangiopancreatography. Preliminary data suggest that cholangioscopy has significant utility in assessment and management of primary sclerosing cholangitis. Applications in posttransplant patients and for selective duct access remain minimally defined and used.