This chapter discusses how to manage a comatose patient with a serious intoxication. Intoxications often present with prominent neurological features, most notably depressed consciousness, delirium, abnormal movements, and seizures. None of these manifestations are specific for any single toxin. Recognition of the most common toxidromes can guide management and predict complications. Early management focuses on securing the airway, ensuring adequate oxygenation, achieving hemodynamic stabilization, excluding hypoglycemia, and considering gastrointestinal decontamination. Options for antidotes, dialysis, and other measures to correct laboratory abnormalities are concisely reviewed in the chapter.