The submucosal tunneling technique was originally developed to provide safe access to the peritoneal cavity for natural orifice transluminal endoscopic surgery procedures. With this technique, the submucosal tunnel becomes the working space for partial myotomy and tumor resection. The submucosal space has come to represent the “third space” distinguished from gastrointestinal lumen (first space) and peritoneal cavity (second space). New applications continue to be developed and further clinical applications in the future are anticipated. This article summarizes the current applications of submucosal tunneling endoscopic resection for subepithelial tumors and describes other related uses of submucosal tunneling.