Tremendous advances have been made in recent years addressing the key obstacles to safe performance and introduction of human natural orifice transluminal endoscopic surgery (NOTES). Animal studies have focused on identifying optimal solutions to these obstacles, in particular methods of creating transluminal access, safe closure of the point of access, and development of a multitasking platform with dedicated instruments. Whether the performance data generated from these animal studies can be reproduced in humans has yet to be determined. Reports of human NOTES procedures are emerging, and the possibility of accomplishing human NOTES based on existing technology has been demonstrated. However, dedicated platforms and devices are still lacking to allow for pure NOTES procedures, and whether NOTES can deliver the postulated benefits of earlier recovery and improved cosmesis remains uncertain.