Over the past few decades gastrointestinal endoscopy has developed from a purely diagnostic technique to one having numerous therapeutic gastrointestinal applications. Simultaneously, minimal invasive surgery is increasingly replacing traditional open abdominal procedures. These trends have led to a new and innovative way of accessing the peritoneal cavity through the orifices of the body (mouth, anus and vagina) by means ofendoscopic surgery: natural orifice translumenal endoscopic surgery (NOTES). Thanks to excellentcollaboration between surgeons and gastroenterologists and experimental animal research, NOTES has developed extremely rapidly over the past few years. Although many limitations need to be surmounted before NOTES can reach the human clinical trial stage, the prospect of safe, minimal invasive and scar-less surgery appears very promising. The near future will tell whether current barriers will be broken down and NOTES will acquire a fixed place in the diagnostic and therapeutic work-up of certain gastrointestinal afflictions.