Endoscopic mucosal resection (EMR) is a major advance in endoscopy for treatment of patients with superficial esophageal, gastric, or colonic lesions, providing a nonsurgical treatment option for management of these lesions. With the assistance of endoscopic ultrasonography, it is now possible to obtain an accurate histologic diagnosis, confirm the depth of the lesion, and in many cases resect submucosal tumors. The main goal of EMR using the advances in endosonography is to detect early gastrointestinal cancers and successfully resect them, offering an outpatient, nonsurgical treatment option. Although popular in the Orient, where there is a high incidence of superficial neoplasia, limited data are available on the use of EMR in the United States. Gastrointestinal (GI) endoscopy nurses and assistants play important roles in successful EMR. This article informs GI staff on the indications for EMR, the procedure and accessories needed, the different resection methods, possible complications, and nursing care.