Access to the abdominal cavity is required for diagnostic and therapeutic endeavors for a variety of medical and surgical diseases. Historically, abdominal access has required a formal laparotomy to provide adequate exposure. Natural orifice transluminal endoscopic surgery (NOTES) is an emerging experimental alternative to conventional surgery that eliminates abdominal incisions and incision-related complications by combining endoscopic and laparoscopic techniques to diagnose and treat abdominal pathology. During NOTES, commercially available flexible video endoscopes are used to create a controlled transvisceral incision via natural orifice access to enter the peritoneal cavity. Common incision-related complications such as wound infections, incisional hernias, postoperative pain, aesthetic disdain, and adhesions could be minimized or eliminated by NOTES. NOTES has evolved from more than 2 centuries of technological innovations and continued growth in the field of surgical endoscopy. Innovative surgical endoscopists have slowly developed means to surpass the constraints of the gastrointestinal lumen by using a flexible endoscope. The future of surgical endoscopy may be the shared entity of NOTES, which further integrates endoscopy, gastroenterology, and minimally invasive and general surgery. Although the promise of NOTES is electrifying to surgeons and endoscopists, several key issues need to be characterized prior to the incorporation of NOTES into routine practice. This article reviews the status, contemporary body of literature, limitations, and potential future implications accompanying the development of NOTES.