Since natural orifice transluminal endoscopic surgery (NOTES) was first described by Anthony Kalloo, it has attracted tremendous interest from surgeons and gastroenterologist all around the world. This special issue of the World Journal of Gastrointestinal Surgery explores the current possibilities and future potential of the most disruptive revolution in the field of surgery represented by the NOTES approach. In the future, new technologies developed for this approach and deeper insight into several gastrointestinal diseases will lead to the design of completely new interventional procedures and change the way we will operate, bringing us to the previously unimaginable goal of “no scar surgery”.