In POTS patients, multiple mechanisms have been proposed to explain the exaggerated increase in heart rate. The orthostatic tachycardia could be a compensatory phenomenon to hypovolemia, impaired sympathetic-mediated vasoconstriction or increased vascular compliance. The later could induce an exaggerated fluid shift upon standing from thorax to lower body. Depending on the mechanism involved different POTS phenotype has been described: (i) hypovolemic POTS; (ii) neuropathic POTS; and (iii) POTS associated with Ehlers-Danlos and joint hypermobility syndrome (EDS/JHS). Of note, there is overlapping in the pathophysiology of POTS with patients having more than one etiology.