In this issue of Gastrointestinal Endoscopy Clinics of North America, guest editor Dr. Amrita Sethi brings her considerable expertise to the topic of Submucosal and Third Space Endoscopy. Endoscopic submucosal dissection (ESD) is now recognized as one of the preferred treatment modalities for premalignant gastrointestinal epithelial lesions and early gastric cancer without lymph node metastasis. ESD techniques require advanced skills, and this issue brings together top experts in the field who provide the information endoscopists need to improve these skills.