Many diverse pathologic processes can involve the sphenoid bone because of its complex embryologic origin. In addition to primary neoplasia, the central location of the sphenoid predisposes it to involvement by many intracranial and extracranial lesions. The presence of multiple foramina and fissures offer "paths of least resistance" that allow the spread of pathology across the skull base. Sphenoid sinus disease also accounts for a number of pathologic entities occurring in this vicinity. This article reviews the more common lesions affecting the sphenoid bone as well as their CT and MR appearance.