Since the first transgastric natural orifice transluminal endoscopic surgery was described, various applications and modified procedures have been investigated. Transgastric natural orifice transluminal endoscopic surgery for periotoneoscopy, cholecystectomy, and appendectomy all seem viable in humans, but additional studies are required to demonstrate their benefits and roles in clinical practice. The submucosal tunneling method enhances the safety of peritoneal access and gastric closure and minimizes the risk of intraperitoneal leakage of gastric air and juice. Submucosal tunneling involves submucosal tumor resection and peroral endoscopic myotomy. Peroral endoscopic myotomy is a safe and effective treatment option for achalasia, and the most promising natural orifice transluminal endoscopic surgery procedure. Endoscopic full-thickness resection is a rapidly developing natural orifice transluminal endoscopic surgery procedure for the upper gastrointestinal tract and can be performed with a hybrid natural orifice transluminal endoscopic surgery technique (combining a laparoscopic approach) to overcome some limitations of pure natural orifice transluminal endoscopic surgery. Studies to identify the most appropriate role of endoscopic full-thickness resection are anticipated. In this article, I review the procedures of natural orifice transluminal endoscopic surgery associated with the upper gastrointestinal tract.