Sporadic colorectal cancer often develops from premalignant lesions, which can be removed before an invasive carcinoma appears. Screening colonoscopies and polypectomies aim to detect and destroy precancerous lesions effectively, while larger polyps may require segmental resections or advanced techniques. Endoscopic submucosal dissection (ESD) has emerged as a valuable advanced approach for removing large colorectal polyps, despite the technical challenges posed by the thickness of the colorectal wall, colonic folds, flexures, and peristalsis. The possibility of preventing colorectal cancer and the increasing demand for minimally invasive procedures have led to a growing interest in advanced polypectomy techniques for colorectal lesions, including ESD. Moreover, ESD offers benefits such as shorter hospital stay, less postoperative pain, and lower rates of mortality and morbidity compared to major surgeries. This chapter provides an in-depth review of the advanced endoscopic resection technique of ESD, including its indications, technical steps, and outcomes.