Natural orifice transluminal endoscopic surgery refers to the method of accessing the abdominal cavity through a natural orifice under endoscopic visualization. Since its introduction in 2004, numerous reports have been published describing different surgical interventions. Recently, a group of expert laparoscopic surgeons and endoscopists outlined the limitations of this approach and issued recommendations for progress toward human trials. Herein we review the published data and propose a series of questions to be considered for future investigations. We also address the controversy involved in the incorporation of this new technology into surgical practice.