Alongside the past development of endoscopic sinus surgery, knowledge about the anatomy of the sinuses has become crucial for surgeons. The sphenoid sinus is one of the most variable of all sinuses. Its relations to vital vascular and nervous elements make its approach a challenge for endoscopic surgeons. These relations include the internal carotid artery, the optic nerve, the pituitary gland, the Vidian nerve, and other vascular and nervous elements depending on the size of the sinus. This paper will make a review of these anatomical relations and their importance in endoscopic sphenoid surgery.