In vivo functional brain imaging provides an opportunity to quantify and localize functional deficits associated with Alzheimer's disease (AD), in relation to dementia severity and heterogeneous cognitive profiles. Such imaging also provides a basis for distinguishing AD from other causes of dementia and for making an early diagnosis of disease. One imaging modality that can elucidate AD is positron emission tomography (PET), which is used to measure regional cerebral metabolic rates for glucose (rCMRglc) and regional cerebral blood flow (rCBF). Resting-state measurements with PET, when related to cognitive profiles in longitudinal studies, indicate that specific cognitive defects are preceded and predicted by reductions in rCMRglc in regions subserving the cognitive functions tested. Metabolic reductions and right/left metabolic asymmetries can be used to convert a “possible” to a “probable” diagnosis of AD by the National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria. Furthermore, discriminant analyses of PET metabolic patterns can identify patients at risk for AD with mild memory deficits as having probable AD. In the future, stimulation PET studies should augment the power of this discriminant analysis.