A paradigm shift in therapeutic endoscopy occurred with the advent of mucosectomy for the treatment of mucosal neoplasms and suture plication for gastroesophageal reflux disease. The objectives changed from finding simple, easy, and quick alternatives to surgery to reproducing surgical results. A radical version of flexible endoscopy has emerged to meet new goals of full-thickness resections, creation of anastomoses, and lumen reconfiguration. This will require a new generation of endosurgical tools that cut, stitch, and staple with added dimensions of multiaxis orientation and triangulation.