Background Natural orifice translumenal endoscopic surgery (NOTES) is a technique that uses transvisceral access to perform surgical procedures entirely through a natural orifice. Despite the increasing awareness of NOTES, there remain obstacles to its technical feasibility and widespread acceptance. Furthermore, with the paucity of high-level supporting evidence, NOTES currently remains an experimental technique. Objective This article reviews the goals, applications, technical and practical challenges, and future direction of NOTES in gastrointestinal surgery.