The manifestations of drug overdose can be complex and result in a variety of physiological effects. Drug overdose situations involving multiple agents further confuse the clinical picture. The clinician must be able to diagnose and treat the patient to prevent unnecessary morbidity or mortality. Often the risk of treating drug overdose with an additional pharmacological agent outweighs the potential benefit. In these cases, the best treatment may involve observation alone. This review describes the current diagnostic and management techniques for the drug overdose patient. Specific drug groups that are commonly used for overdose are discussed with emphasis on physiological manifestations of intoxication and poisoning and the potential for delayed effects. Treatment options for various groups are also discussed. It appears that invasive procedures such as gastric lavage and whole-bowel irrigation are not appropriate for the majority of overdose situations. The use of oral activated charcoal may also be of limited value. As specific antidotes for drug overdose are not widely available, supportive treatment must be based on the individual patient.