In mild or atypical cases of Alzheimer's disease (AD) the differential diagnosis to other dementing diseases, such as vascular dementia (VD), may pose a difficult problem. Beside computed tomography (CT) and magnetic resonance imaging (MRI), functional neuroimaging by positron emission tomography (PET) support the clinical diagnosis by visualizing cerebral function. PET of 18F-2-fluoro-2-deoxy-D-glucose (FDG) for measurement of regional cerebral glucose metabolism (rCMRGl) has shown a typical metabolic pattern in patients with probable AD: hypometabolism in temporoparietal and frontal association areas, but relative recessing of primary cortical areas, basal ganglia and cerebellum. In VD a different pattern is seen. It consists of scattered areas with reduction of rCMRGl typically extending over cortical and subcortical structures. Severity of dementia is correlated with rCMRGl reduction in the temporoparietal association cortex, irrespective of the cause of dementia. Also the total volume of hypometabolic regions is related to severity of dementia but did not differ between AD and VD, even in patients with small lacunar infarction. This indicates that the total volume of functional tissue loss is more important since it also includes the effects of incompletely infarcted tissue and morphologically intact but deafferented cortex. The characteristic metabolic pattern has a high diagnostic accuracy for the discrimination between probable AD, normals and VD, even in patients with mild cognitive impairment. Under clinical and therapeutic aspects the analysis of longitudinal changes of rCMRGl has shown that neuropsychological and metabolic changes are closely related in both, AD and VD.