Pure autonomic failure is an uncommon, idiopathic neurodegenerative disorder with primarily peripheral autonomic manifestations. The onset and progression of symptoms are gradual, and the presenting feature is characteristically orthostatic hypotension. Other commonly reported features of autonomic failure include constipation, bladder dysfunction, erectile dysfunction, and sweating abnormalities. The disorder is one of the alpha-synucleinopathies, a heterogenous group of disorders characterized by abnormal accumulation of the presynaptic protein, alpha-synuclein, in the central and/or peripheral nervous system. Although the initial presentation may be one of isolated peripheral autonomic impairment, over a period of time, some patients may develop motor and cognitive deficits that indicate central neuronal degeneration, and a phenotype consistent with one of the central alpha-synucleinopathies, Parkinson’s disease (PD), dementia with Lewy bodies, or multiple system atrophy.