The central autonomic network includes the insular cortex, anterior cingulate cortex, amygdala, hypothalamus, periaqueductal gray, parabrachial nucleus, nucleus of the solitary tract, ventrolateral reticular formation of the medulla, and medullary raphe. These areas: are reciprocally interconnected; receive converging visceral and somatosensory information; generate stimulus-specific patterns of autonomic, endocrine, and motor responses; and are regulated according to the behavioral state, including the sleep–wake cycle. Several components of the central autonomic networks are affected in neurodegenerative disorders characterized by the presence of intracellular inclusions containing α-synuclein. These include multiple system atrophy (MSA), characterized by accumulation of glial cytoplasmic inclusions, and Lewy body disorders, including Parkinson disease (PD), dementia with Lewy bodies, and the so-called “pure” autonomic failure. In MSA, involvement of the rostral ventrolateral medulla may be primarily responsible for orthostatic hypotension; involvement in the pontine micturition area, sacral preganglionic nucleus, and Onuf nucleus is responsible for neurogenic bladder; and involvement of the pre-Bötzinger complex and medullary raphe may contribute to sleep-related respiratory abnormalities. In contrast, Lewy body disorders are characterized by early involvement of the enteric nervous system and cardiac sympathetic ganglia. The dorsal motor nucleus of the vagus is affected both in MSA and at early stages of PD.