Natural orifice translumenal endoscopic surgery (N.O.T.E.S) is a technique that allows access to the peritoneal cavity through natural orifices (oral, rectal, vaginal, vesical) without passing through the anterior abdominal wall. Rapid strides have been made in developing this technique, especially in animal models. Majority of research work in this field is originating from USA, while human clinical trials are being reported from India and Southern America. Morbidly obese patients and ITU patients are two target groups where N.O.T.E.S if implemented, will have the highest potential and bearing. With increasing evidence of safe practice in human models, questions on indications and feasibility of practice need to be addressed by rigorous research, strong evidence and collaboration between surgical centers worldwide.