A complication of severe brain injury is a syndrome of intermittent agitation, diaphoresis, hyperthermia, hypertension, tachycardia, tachypnea, and extensor posturing. To capture the main features of this syndrome, derived through literature review and our own case series, we propose the term paroxysmal autonomic instability with dystonia. We reviewed reports of autonomic dysregulation after brain injury and extracted essential features. From the clinical features, consistent themes emerge regarding signs and symptoms, differential diagnosis, and pharmacological therapies. We used these findings to make recommendations regarding diagnosis and treatment. Paroxysmal autonomic instability with dystonia appears to be a distinctive syndrome after brain injury that can mimic other life-threatening conditions. Early recognition may lead to fewer diagnostic tests and a rational approach to management. Prospective trials of specific drugs are needed to determine optimal efficacy.