This article provides a broad theoretical and clinical overview of the three regional prefrontal syndromes. An understanding of the extended neural connectivity of the prefrontal cortex provides the template for describing the three distinct prefrontal syndromes (dysexecutive, disinhibited, and apathetic types), each associated with dysfunction in one of the three prefrontal regions. This clinical approach should aid the clinician in determining the etiology of the specific regional prefrontal syndrome and developing effective treatment strategies.