Antipsychotics include the ‘typical’ agents (phenothiazines, thioxanthines, and butyrophenones) as well as the more recently introduced agents referred to as ‘atypical’ (dibenzodiazepines, diphenylbutylpiperidines and benzamides). There are significant differences between these drugs in their toxicity in overdose. For example, thioridazine has been observed to be more cardiotoxic in overdose than other antipsychotic drugs, whereas clozapine and loxapine are the most likely to cause seizures. Many antipsychotic overdoses will result in mild sedation and no other ill effects. Most patients can be safely discharged 6 hours after the poisoning, but it is critical to recognize the more seriously poisoned patient who will develop cardiotoxicity or seizures. These patients have ECG changes (QRS and/or QT prolongation) and decreased level of consciousness and therefore require intensive care unit admission. Treatment of antipsychotic overdose includes supportive care of the comatose patient, effective gastrointestinal decontamination with activated charcoal, intravenous fluids, and ECG monitoring. Cardiotoxicity in antipsychotic overdose may manifest as ventricular arrhythmia, various degrees of conduction delay, or hypotension. The primary treatment of cardiotoxicity is plasma alkalinization with sodium bicarbonate and hyperventilation. Neurotoxicity is manifest as coma and seizures. Treatment consists of intubation, hyperventilation, and plasma alkalinization.