Functional imaging studies with positron emission tomography (PET) and single photon emission computed tomography (SPECT) have shown alterations in glucose metabolism, perfusion, dopaminergic systems, cholinergic systems and activation of microglia in the brains of patients with Parkinson's disease (PD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and multiple system atrophy (MSA). [18F]fluorodeoxyglucose-PET and perfusion SPECT show characteristic changes in brain glucose metabolism and perfusion, which are useful for differential diagnosis of these disorders. [18F]dopa-PET and SPECT studies of dopamine transporters show marked impairment of nigrostriatal neuronal terminals in PD, PSP, CBD and MSA. PET studies with carbon-11-labeled acetylcholine analogs have shown mild to moderate reduction of acetylcholinesterase (AChE) activity in the cerebral cortex in PD, severe reduction of AChE activity in the thalamus in PSP, and marked reduction of AChE activity in the cerebellum. [11C](R)-PK11195-PET studies have shown an increase in activated microglia in brain regions that mirror the known distribution of neuropathologic changes in PD, CBD and MSA, which provides insight into the pathophysiology of these disorders.