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Natural orifice translumenal endoscopic surgery (NOTES) involves the intentional perforation of the viscera with an endoscope to access the abdominal cavity and perform an intraabdominal operation. In a brief time period, NOTES has been shown to be feasible in laboratory animal and human studies. Easy access to the peritoneal cavity and complete gastric closure should be secured before NOTES can be recommended as an acceptable alternative in clinical practice. The concept of submucosal endoscopy has been introduced as a solution to overcome these two primary barriers to human NOTES application. Its offset entry/exit access method effectively prevents contamination and allows the rapid closure of the entry site with a simple mucosal apposition. In addition, it could be used as an endoscopic working space for various submucosal conditions. Herein, the detailed procedures, laboratory results and human application of the submucosal endoscopy will be reviewed.