Indications for Natural Orifice Transluminal Endoscopic Surgery or NOTES have so far mainly concerned intra-abdominal surgery. The next question to be addressed was whether this access can be extended into other body cavities and, in particular, whether there is a significant role for NOTES above the diaphragm? Using the esophagus, one of the mediastinal organs, as a direct carrier to access the mediastinum and the pleural cavity would eliminate the dissection of the pretracheal fascia required by mediastinoscopy and would give access to the inner part of lung parenchyma. Alternatively, transgastric (or even transvaginal) transhiatal approaches could supplement standard operative techniques in order to minimize abdominal wall ingression. Furthermore, conventional techniques seem disproportionate measures for relatively simple procedures such as evaluating the outcome of chemotherapy and restaging of medically treated mediastinal lesions. As a truly minimal access technique, NOTES could therefore find new indications for intervention. The obvious limiting factor in all of this is assurance of 'leak proof' mural closure. However, if safety of access-site sealing can be established in clinical studies, we could have found an easier, reproducible alternative to the access to mediastinum. This review examines the rationale and evidence for proposing such a venture and deliberates its likely clinical applicability and thereby its potential to become a reality.