For many, the excitement and eventually the acceptance of third space endoscopy began with the peroral endoscopic myotomy (POEM). The submucosal dissection technique that defines this procedure was initially developed as a method for facilitating natural orifice transluminal endoscopic surgery (NOTES). Although most NOTES procedures failed to gain widespread acceptance, the submucosal tunneling technique was repurposed as a key aspect of facilitating the POEM procedure. In this chapter, we will explore origins, define indications, detail procedural techniques, and analyze outcomes of the procedure that launched third space endoscopy into the mainstream: POEM.