Orthostatic hypotension (OH) is a cardinal sign of cardiovascular (CV) autonomic dysfunction as a result of autonomic nervous system failure to control the postural hemodynamic homeostasis. The proportion of individuals with OH increases with aging and chronic conditions, such as neurodegenerative diseases, hypertension, heart failure, diabetes, renal dysfunction, autoimmune diseases, and cancer. In individuals over 70 years of age, more than 20% can be affected. It is now increasingly recognized that there is a direct relationship between OH and each step of the CV disease continuum, eventually leading to end‑stage heart disease and CV death. In particular, prevalent OH is associated with cardiac functional and structural remodeling, left ventricular hypertrophy, elevated levels of circulating markers of inflammation, increased intima‑media thickness, subclinical atherosclerosis, and thrombosis. Beyond subclinical changes, the presence of OH independently predicts coronary events, stroke, atrial fibrillation, heart failure, and CV mortality. Furthermore, OH is associated with syncope, falls, and fragility fractures, presenting hurdles to be overcome in the delivery of the best management of CV risk factors. Taken together, OH heralds disruption of global circulatory homeostasis and flags overt autonomic dysfunction. The presence of OH is also an independent risk factor for mortality and CV disease; however, until now, the importance of this highly prevalent disorder has been given insufficient attention by clinicians and other healthcare providers. Consequently, more studies are needed to find effective treatment for this troublesome condition and to identify preventive measures that could reduce the burden of CV risk in OH and autonomic dysfunction.