Postural tachycardia syndrome (POTS) refers to the presence of orthostatic intolerance symptoms with a heart rate increment ≥ 30 bpm, usually up to ≥ 120 bpm. Pathophysiology and POTS's clinical presentation are heterogeneous and its prognosis is uncertain. We reviewed the major clinical characteristics of POTS patients and assessed their long-term follow-up. Our series results, one with the longest follow-up, illustrate POTS as a clinical entity with variable, but usually benign outcome, in which most patients can reassume their daily activities without great limitations, after proper diagnosis and treatment are made.