PET is potentially the most powerful tool yet available for the direct, in vivo investigation of the biologic basis of psychiatric and neuropsychiatric disorders. The fulfillment of its potential rests on the development of methodologies and study design appropriate to psychiatric disorders. To date, findings in both schizophrenia and affective disorder, using protocols largely based on resting state data acquisition, suggest altered regional metabolism. These approaches need to be extended, particularly by the application of protocols that utilize PET to obtain longitudinal data under controlled experimental situations. In two conditions traditionally ascribed to psychologic causes, OCD and PD, there is intriguing evidence of specific biologic abnormalities, which, if confirmed, would lead to a fundamental revision of their nosologic status. In neuropsychiatric disorders PET findings, although preliminary in nature, offer an alternative paradigm to traditional clinicopathologic correlations by suggesting that clinical impairments relate to physiologic effects at sites distant from structural lesions.