Human natural orifice translumenal endoscopic surgery (NOTES) is already being reported from numerous centers, and the results seem promising. There are key issues to be addressed and benefits over traditional safe procedures need to be demonstrated. Interestingly, however, human NOTES seem to be progressing at a fast pace compared with the evolution of surgical procedures or techniques described previously. This article examines the current status of NOTES in humans, the challenges, and the implications on the future of minimal access surgery.