Cyclic antidepressant drug toxicity is a common cause of death from prescription drug overdose in the United States. The pathophysiologic features include cardiac, neurologic, and gastrointestinal effects. Major signs of toxicity are identifiable in the emergency department. Treatment includes aggressive supportive care, activated charcoal, alkalinization therapy, and management of arrhythmias, hypotension, and seizures. Outcomes are generally good when early appropriate treatment is initiated.