Although most patients with concussion recover within days to weeks, a small but significant minority develop persistent signs and symptoms of post-concussion syndrome (PCS). The standard treatments of PCS, rest and cognitive adaptation, have limited effectiveness. PCS patients are advised not to exercise because of the concern for symptom exacerbation. Prolonged rest, however, leads to deconditioning (especially in athletes) and may cause secondary effects including depressive symptoms. Concussion is associated with metabolic and physiological changes in the brain and in other organ systems (for example, autonomic function of the heart and altered cerebral autoregulation, sleep, and circadian rhythms). We propose that PCS results from ongoing central and systemic physiologic regulatory dysfunction after traumatic brain injury (TBI) and we further propose that this physiologic dysfunction may be reduced or alleviated by individualized controlled sub-symptom threshold aerobic exercise rehabilitation.