Purpose of Review <p>Endoscopic retrograde cholangiopancreatography is an advanced endoscopic procedure used mainly for the purpose of biliary intervention. During an ERCP a duodenoscope is used to assess the ampulla of Vater to inject contrast medium into the common bile duct through biliary cannulation. Biliary cannulation can be challenging, with studies showing unsuccessful biliary cannulation with standard technique greater than 10%. Needle-knife fistulotomy is a unique precut sphincterotomy technique that can assist with difficult biliary cannulation.</p> Review of Findings <p>Needle-knife fistulotomy has transitioned from a “last-ditch” technique to sometimes a primary approach in select patient populations by endoscopists. The major impetus for this change is due to consistent results showing a lower risk of post-ERCP pancreatitis compared to other pre-cut methods.</p> Summary <p>This review article will go in-depth on the technique of needle-knife fistulotomy, the benefits and suspected complications of needle-knife fistulotomy compared to traditional sphincterotomy techniques and the evolution of NKF as a first-choice option for biliary cannulation.</p>