The concept of natural orifice translumenal endoscopic surgery (NOTES) has grown in acceptance since the time of its introduction in 2000. Developments in techniques of peritoneal access and closure, surgical techniques, and equipment modification have already been published and intensive research is ongoing. Current and future endoscopists will reap the benefit of this research because many techniques and devices that are developed for NOTES will enhance the ability to perform luminal intervention, including polypectomy, endoluminal hemostasis, and submucosal resection. The authors attempt to predict the future of NOTES by describing potential applications for certain clinical scenarios and conditions.