The superior orbital fissure is a critical three-dimensional space connecting the middle cranial fossa and the orbit. From an endoscopic viewpoint, only the medial aspect has a clinical significance. It presents a critical relationship with the lateral sellar compartment, the pterygopalatine fossa and the middle cranial fossa. The connective tissue layers and neural and vascular structures of this region are described. The role of Muller's muscle is confirmed, and the utility of the maxillary and optic strut is outlined. Muller's muscle extends for the whole length of the inferior orbital fissure, passes over the maxillary strut and enters the superior orbital fissure, representing a critical surgical landmark. Dividing the tendon between the medial and inferior rectus muscle allows the identification of the main trunk of the oculomotor nerve, and a little laterally, it is usually possible to visualize the first part of the ophthalmic artery. Based on a better knowledge of anatomy, we trust that this area could be readily addressed in clinical situations requiring an extended approach in proximity of the orbital apex.