After the first report by Kalloo et al on transgastric peritoneoscopy in pigs, it rapidly became apparent that there was no room for an under-evaluated concept and blind adoption of an appealing (r)evolution in minimal access surgery. Systematic experimental work became mandatory before any translation to the clinical setting. Choice and management of the access site, techniques of dissection, exposure, retraction and tissue approximation-sealing were the basics that needed to be evaluated before considering any surgical procedure or study of the relevance of natural orifice transluminal endoscopic surgery (NOTES). After several years of testing in experimental labs, the revolutionary concept of NOTES, is now progressively being experimented on in clinical settings. In this paper the authors analyse the challenges, limitations and solutions to assess how to move from the lab to clinical implementation of transgastric endoscopic cholecystectomy.