The authors reviewed the two most common current uses of brain 18F-labeled fluoro-2-deoxyglucose positron emission tomography (FDG-PET) at a large academic medical center. For epilepsy patients considering surgical management, FDG-PET can help localize epileptogenic lesions, discriminate between multiple or discordant EEG or MRI findings, and predict prognosis for post-surgical seizure control. In elderly patients with cognitive impairment, FDG-PET often demonstrates lobar-specific patterns of hypometabolism that suggest particular underlying neurodegenerative pathologies, such as Alzheimer's disease. FDG-PET of the brain can be a key diagnostic modality and contribute to improved patient care.