The central skull base region represents a complex intersection between the intracranial compartment, the osseous foundation of the skull base, the orbits, the paranasal sinuses, and the suprahyoid neck. A modern radiologic approach to this region should take into account the 3-dimensional complexity of the region as well as the cross-sectional anatomical detail available to today's radiologist. This analytical approach should permit identification of lesional anatomical subsites, establishment of lesional origins, and allow for an anatomy-based differential diagnosis. In this article, we define a practical central skull base region that includes structures that directly affect neuroimaging of this dense landscape. By reframing the boundaries, the central skull base region becomes comprehensive, emphasizing the natural tendency for pathologic processes to involve contiguous anatomical subunits, and underscores the complexity and challenges of this region for neuroimaging specialists. © 2013 Elsevier Inc.