Endoscopic submucosal dissection (ESD) is an advanced endoscopic technique pioneered by the Japanese, for en bloc removal of large gastrointestinal epithelial lesions. This technique involves injection of a solution into the submucosal layer, followed by dissection around and then under the lesion, with separation of the submucosal layer using an electrocautery knife. ESD technique allows the endoscopist to visualize and control the depth of dissection. Originally described for early gastric cancer, the indications and techniques have evolved to include lesions in most locations and layers of the gastrointestinal wall. Western endoscopists have recently adopted this technique as well. From a practice standpoint, ESD provides the endoscopist with the ability to remove large superficial tumors in a single piece, including ulcerated lesions, lesions with submucosal fibrosis, recurrent neoplasms, non-lifting lesions, and potentially lesions with very early submucosal invasion. En bloc resection and curative resection rates are high in the eastern literature, with bleeding, perforation and strictures, the most frequently reported complications. The procedure is difficult and time consuming, with a steep learning curve and significant complication rates, and therefore requires specialized training.