The topics covered in this issue, an update from what was first published in the Gastrointestinal Endoscopy Clinics in 2008, reflect the fact that NOTES is seeing a resurgence in popularity. Now, eight years later, there is more data to confirm safety, to look at the best options for using natural orifices, and to talk about optimal training scenarios. The Guest Editor has enlisted some of the top experts on NOTES to contribute articles devoted to Seminal Developments: SM Tunnel Technique; Peroral Endoscopic Myotomoy (POEM); Submucosal Tumor Endoscopic Resection; Endoscopic Full Thickness Resection; Submucosal Tunneling for NOTES Procedures Beyond Resection; Pyloromyotomy; New NOTES: Western Perspective; and Why Did the Old NOTES Fail: Lessons Learned that can Guide New NOTES Development.