Paroxysmal sympathetic hyperactivity is a syndrome associated with brain trauma, stroke, encephalitis, and other forms of brain injury. It is characterized by uncontrolled episodes of unbalanced sympathetic surges causing hyperthermia, diaphoresis, tachycardia, hypertension, tachypnea, and dystonic posturing. Patients who develop paroxysmal sympathetic hyperactivity have worse neurologic outcomes, longer hospital stays, and more complications. Despite the clear negative impact on outcome, consensus regarding diagnostic criteria, risk factors, pathophysiology, and treatment approaches is lacking. Recently, the importance of consensus regarding diagnostic criteria has been emphasized, and new theories of pathophysiology have been proposed. Many treatment options are available, but only a few systemic studies of the efficacy of treatment algorithms exist. Treatments should focus on decreasing the frequency and intensity of episodes with regularly scheduled doses of medications, such as long-acting benzodiazepines, nonselective β-blockers, α2-agonists, morphine, baclofen, and gabapentin, usually in combination. Treatment of acute breakthrough episodes should focus on doses of as-needed morphine and short-acting benzodiazepines. A balance between control of symptoms without oversedation is the goal.