Since its inception nearly 40 years ago, endoscopic retrograde cholangiopancreatography (ERCP) has become the therapeutic cornerstone for removal of common bile duct (CBD) stones. Removal of the vast majority of stones with endoscopic sphincterotomy (EST), followed by sweeping the duct with either balloon or basket is successful in most cases, with an acceptable safety profile. Nevertheless, despite considerable refinements in ERCP over the last four decades, management of large, ‘‘difficult’’ CBD stones remains a therapeutic challenge. The definition of ‘‘large’’ CBD stones varies, ranging from[1 to[2 cm in diameter. Although the size of a stone is a prime determinant of its resistance to extraction, factors other than size are important. In a multivariate analysis, acute angulation of the distalmost aspect of the CBD and a shorter length of this distal CBD ‘‘arm’’ were associated with difficulty of ductal clearance [1]. Other factors inversely associated with stone clearance include very large stones such as those [3 cm, surgically altered anatomy, and firmness of the stones. The endoscopist must also consider not only the absolute stone size, but its diameter relative to the width of the distal duct through which it must be removed. Several different fragmentation modalities have been studied for the removal of difficult stones: extracorporeal shock wave lithotripsy (ESWL), mechanical lithotripsy (ML), electrohydraulic lithotripsy (EHL), and laser lithotripsy (LL) (Table 1). Each technique works reasonably well, albeit with significant drawbacks. ESWL achieved ductal clearance in 84 % of 283 patients with an acceptable minor complication profile [2]. However, this technique is notoriously cumbersome, requiring multiple treatment sessions: initial ERCP with placement of nasobiliary drain, ESWL with stone fragmentation, followed by at least one additional ERCP with removal of smaller stone fragments. A randomized study comparing LL with ESWL showed that LL cleared the duct with fewer fragmentation sessions and endoscopic procedures [3]. Mechanical lithotripsy (ML) has a long track record in the therapy of large stones. It utilizes a metal basket and overlying sheath, into which stone fragments become trapped and crushed. Its advantage is that it is a widely available accessory which can be deployed in the course of a ‘‘routine’’ ERCP without bringing in additional, expensive equipment. However, it can be challenging to set up and deploy; furthermore, its use does not entirely prevent the feared scenario of impacted basket and stone in the biliary tree, which transforms an endoscopic dilemma into a surgical emergency. Results are generally favorable, but not universally successful. In a review from a Canadian referral center, nearly one-quarter of patients treated with ML required more than one endoscopic treatment [4]. Electrohydraulic lithotripsy (EHL) relies upon the generation of shock waves, which under continuous saline irrigation of the bile duct are transmitted to stones, which then shatter. It has been traditionally performed using a dedicated smaller caliber cholangioscope which fits inside the working channel of a therapeutic duodenoscope, a so-called ‘‘mother–baby’’ scope arrangement. Unfortunately, this arrangement is extremely time-consuming, requires two endoscopists, and the cholangioscopes are extremely fragile. These formidable barriers have detracted from the appeal of EHL, even in tertiary referral centers. Laser lithotripsy (LL) works on a similar general principle to EHL. LL uses a high power light wavelength to deliver shockwaves to stones, thereby fragmenting them. S. J. Heller (&) Division of Gastroenterology, Fox Chase Cancer Center, Philadelphia, PA, USA e-mail: Stephen.Heller@fccc.edu