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. Contains 15 practice-oriented topics including building the toolbox of devices to optimize a practice in submucosal endoscopy; understanding the principles of electrocautery for submucosal endoscopy; endoscopic submucosal dissection in the colon and rectum; techniques for peroral endoscopic myotomy, from mouth to anus; management of adverse events of submucosal endoscopy; and more. Provides in-depth clinical reviews on submucosal and third space endoscopy, offering actionable insights for clinical practice. Presents the latest information on this timely, focused topic under the leadership of experienced editors in the field. Authors synthesize and distill the latest research and practice guidelines to create clinically significant, topic-based reviews.