The postural tachycardia syndrome (POTS) is characterized by excessive orthostatic tachycardia with chronic symptoms that are associated with upright posture. These chronic symptoms (of at least 6 months' duration) include tachycardia, exercise intolerance, lightheadedness, extreme fatigue, headache, and mental clouding. Patients with POTS demonstrate an increase in heart rate of at least 30 beats/min within 5 to 30 minutes of assuming an upright posture, in the absence of orthostatic hypotension (a fall in blood pressure >20/10 mm Hg) and in the absence of other medical disorders that might cause tachycardia. POTS can be associated with a high degree of functional disability. The blood volume has been found to be low in many patients with POTS. This article will review some of the data regarding blood volume perturbations in POTS, blood volume regulation in POTS, and potential treatment approaches.