The sphenoid bone is the osseous foundation of the central skull base. The body of the sphenoid is cuboid in shape and its posterior margin is joined to the basilar occipital bone (basiocciput) via a synchondrosis to form the complete clivus. Traditionally, radiologic discussions of intrinsic disease of the central skull base emphasize marrow space-occupying lesions including metastatic disease, myeloma, and chordoma. Based on our practical experience and the anatomical boundaries of the central skull-based region put forth, we include lesions of the sphenoid sinus and petrous apex in our discussion. We describe lesions that might originate within, be confined to, or principally involve the skeletal foundation of the central skull base, including the pneumatized regions contained within. Intrinsic lesions affecting the central skull base are emphasized and the most important computed tomography and magnetic resonance imaging findings that allow for effective diagnosis, planning, and treatment are highlighted. © 2013 Elsevier Inc.