The purpose of this paper is to provide a concise, selective review of the major issues and findings germane to structural and functional neuroimaging studies of bipolar affective disorder (BPD). In attempting to identify the brain changes associated with BPD, investigators have used neuroimaging techniques to focus on several interrelated questions. These are: What are the changes and where do they occur? Do their nature and location suggest a particular etiopathologic basis or have notable clinical correlates? With regard to specificity, are the changes unique to BPD, or do they overlap with those reported in other neuropsychiatric illnesses, especially schizophrenia? Do they occur in brain systems that normally play a role in modulating mood? Finally, how do the brain changes integrate with neurocognitive, neurogenetic, and neuropathologic data in the same patients? To date, these questions have been addressed only preliminarily. We outline some of the strategies used to pursue answers to these questions and review conclusions to date.