Sleep disorders are important manifestations of neurodegenerativediseases and sometimes are clinically evident well before the onset of other neurological manifestations. This review addresses theneuroanatomical basis and the mechanisms of sleep regulation in humans in relation to the neuropathology of entities associated with sleep disturbances in selected diseases, including Alzheimer disease, progressive supranuclear palsy, Lewy body disorders, multiple-system atrophy, and fatal familial insomnia. This includes abnormalities of circadian rhythm, insomnia, narcolepsy, rapid eye movements sleep behavior disorders, and excessive daytime sleepiness.