Natural orifice transluminal endoscopic surgery (NOTES) is an exciting concept gaining national attention as a novel and minimally invasive approach to gastrointestinal surgery and endoscopy. The hope of combining the talents and experience of surgeons and gastrointestinal endoscopists with emerging technologies has created enthusiasm for developing this approach as a specialty itself. Upon initial review, many procedures seem to naturally lend themselves to this approach and include endoscopic mucosal resection, small tumor excision, and access to the peritoneum. The main question to be answered in this short article is: What is gained and what is lost with NOTES?