Endoscopic full-thickness resection (EFTR) is a "changing-concept" endoscopic resection technique, which safely allows resecting deep submucosal tumors (SMTs) in the gastrointestinal (GI) wall. It's a highly promising endoscopic procedure that allows full-thickness excision of a small piece of the complete GI wall by using only a flexible endoscope. EFTR is a meeting point between surgery and endoscopy and probably the onset of many prospective combined minimally invasive therapeutic techniques that science will explore. In this review, use of the EFTR technique for gastrointestinal SMTs is highlighted, focusing on some technical aspects, indications, contraindications and outcomes.