| Summary: | Therapeutic endoscopy has evolved tremendously over the past decades and the development of submucosal endoscopy opens the third space for treatment of gastrointestinal diseases. This review focused on the recent development in third space endoscopy, with introduction of its development from peroral endoscopic myotomy (POEM) to beyond. Two recent randomized trials comparing POEM against pneumatic dilation and laparoscopic Heller myotomy (LHM) demonstrated significantly better relief of dysphagia for POEM compared to pneumatic dilation, while POEM achieved similar outcomes compared to LHM. Apart from achalasia, third space endoscopy is now developed to manage spastic esophageal motility disorders, esophageal diverticular diseases, gastroparesis, and Hirschsprung’s disease. Subepithelial tumors can also be resected through tunneling and endoscopic full-thickness resection. In future, third space endoscopy will be one of the major areas in development of diagnostic and therapeutic endoscopy using novel imaging technologies and therapeutic devices.
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