Surgery has rapidly evolved as new technologies are adopted. With the introduction of laparoscopic surgery, patient outcomes have improved, with faster recovery from smaller incisions. In an effort to continually improve these outcomes and offer alternative options to higher risk patients, a number of investigators have proposed the concept of operating in the peritoneal space through natural orifices, obviating the need for any abdominal skin incisions. Natural orifice translumenal endoscopic surgery (NOTES) offers the same advantages as laparoscopic surgery without skin incisions, and possibly without general anesthesia. This article gives a conceptual and technical description of NOTES, discusses its challenges and potential pitfalls, reviews the early efforts at NOTES-specific device development, and predicts potential future directions of this exciting new area of surgery.