Delirium symptoms suggest dysfunction of multiple brain regions. However, little is known about delirium's underlying neuropathogenesis. This article addresses the need for research on neuroanatomic and neuropathophysiologic underpinnings of delirium, analogous to that of schizophrenia and affective disorders. Electrophysiologic tests, structural and functional brain imaging, and neurotransmitter studies in delirium are critically reviewed. The importance of both cerebral cortical and subcortical areas is noted, with emphasis on frontal, right-hemisphere, and subcortical regions, including caudate and anteromedial thalamus. Each symptom of delirium can be viewed from a neuroanatomic and neurochemical perspective. Recommendations for research are made throughout the article.