Postural orthostatic tachycardia syndrome (POTS) is associated with many symptoms including orthostatic intolerance, fatigue, palpitations, and cognitive dysfunction. Treatment, which typically consists of exercise, increased dietary sodium and fluids, compression garments, and medications for orthostatic intolerance, frequently produces unsatisfactory results. The authors report the case of a 26-year-old woman who presented with a 6-year history of severe fatigue, orthostatic intolerance, heat intolerance, cognitive dysfunction, and diffuse pain. She had previously injured her jaw on an obstacle course. Results of a standing test were consistent with POTS. After standard medical therapy was unsuccessful, the patient was referred for osteopathic manipulative treatment. At her 18-month follow-up, the patient's symptoms had improved dramatically. Physicians should consider osteopathic evaluation and manipulative treatment when caring for patients with POTS.