This chapter discusses the diagnosis, evaluation and management of overdoses. It covers a selection of drug overdoses such as acetaminophen, aspirin, tricyclic antidepressants, beta-blockers, calcium channel blockers, and digoxin. In acetaminophen overdose, normal metabolic pathways are saturated and glutathione is depleted, resulting in N-acetyl- p-benzoquinone imin (NAPQI) accumulation and subsequent hepatocellular damage. Aspirin is normally metabolized by the liver through conjugation. In overdose, enzymes become saturated and renal elimination becomes important. In tricyclic antidepressant overdose, transient hypertension is followed by hypotension and bradycardia as catecholamines are depleted. In overdose of beta-blockers, selectivity for beta receptors is lost, and beta 1 and beta 2 effects are seen. Calcium channel blocker toxicity shifts myocardial metabolism from free fatty acids to carbohydrates. Digoxin toxicity can cause lethal ventricular dysrhythmias including ventricular tachycardia, torsades de pointes, and ventricular fibrillation.