<b><i>Background:</i></b> One of the hallmarks of the E-synucleinopathies is the degeneration of the autonomic nervous system. <b><i>Summary:</i></b> This review discusses the diagnosis and management of cardiovascular autonomic failure within the context of the E-synucleinopathies. In addition, it outlines the utility of various laboratory assessments including cardiovascular reflex tests for the differential diagnoses of these disorders, as well as general disease management strategies. <b><i>Key Messages:</i></b> Laboratory investigations assessing the autonomic control of the cardiovascular system are useful in the differential diagnosis of E-synucleinopathies, especially in early stages of disease. <b><i>Clinical Implications:</i></b> The characterization of the different features of AF in patients with E-synucleinopathies is challenging because it might help to improve the accuracy of the differential diagnosis between these diseases at onset. Further cardiovascular AF has been demonstrated to have a negative prognostic role in E-synucleinopathies, therefore an early detection of cardiovascular dysautonomia allows to positively impact the disease course guiding the appropriate therapy. i 2014 S. Karger AG, Basel