Paroxysmal sympathetic hyperactivity after traumatic brain injury is an underappreciated and undertreated condition. It may cause potentially life-threatening complications, such as intracranial hypertension, dehydration, hyperthermia, refractory surges of hypertension, and muscle contractures. The differential diagnosis is broad, but it can be sorted out quickly by a focused evaluation. The difficulties with management and short- and long-term pharmacological approaches are discussed in this chapter. These include boluses of morphine sulfate for aborting the episodes, propranolol and clonidine for control of the tachycardia and hypertension, and baclofen and diazepam for improving increased muscle tone. Gabapentin is useful for achieving control of the sympathetic dysfunction in the long term.