Presenting symptoms of the isolated sphenoid sinus lesion are often vague and non-specific. Diagnostic nasal endoscopy procedures and imaging techniques are of great value for an early and precise diagnosis. Moreover, endoscopic sinus surgery is a safe and effective technique that allows a direct route to the sphenoid sinus. Because of its close vicinity to important and vulnerable structures of the skull base, delay in diagnosis and treatment can be potentially lethal. Endoscopically controlled procedures for the sphenoid sinus provide the surgeon with an obvious alternative to the traditional approaches. From November 1994 to May 2001 the authors operated on 41 patients with isolated sphenoid lesions. The pathology spectrum was rather wide and included 11 cases of isolated fungal sinusitis, 10 mucoceles, 7 bacterial sinusitis, 7 cerebrospinal fluid leaks, 3 inverted papillomas, 1 chondrosarcoma, 1 ossifying fibroma and 1 foreign body. The sphenoid sinus was the only sinus involved, and lesions arising from adjacent tissues were excluded. In this paper, the authors present clinical symptoms, endoscopic findings and imaging data as well as endoscopic surgical techniques for the treatment of sphenoid sinus disease.