Upright posture requires rapid and effective circulatory and neurologic compensations to maintain blood pressure and consciousness. Although it has been recognized over the past 100 years or more that the act of standing may cause hypotension in patients with autonomic dysfunction, only recently several of the pathophysiologic mechanisms resulting in orthostatic intolerance have been discovered. In patients with orthostatic hypotension, failure of reflex vasoconstriction causes pooling of blood in the legs during standing. Not everyone with a postural blood pressure drop requires treatment, nor does everyone with posturally induced symptoms have orthostatic hypotension. This review will discuss current knowledge of a broad, heterogeneous group of disturbances in the autonomic nervous system, each of which is manifested by hypotension, orthostatic intolerance, and often syncope.