Two cases of severe beta-blocker overdose are presented that were treated successfully with glucagon therapy. The effects of glucagon in reversing the cardiovascular depression of profound beta-blockade, including its mechanism of action, onset and duration of action, dosage and administration, cost and availability, and side effects are reviewed. Medical complications of beta-blocker overdose include hypotension, bradycardia, heart failure, impaired atrioventricular conduction, bronchospasm and, occasionally, seizures. Atropine and isoproterenol have been inconsistent in reversing the bradycardia and hypotension of beta-blocker overdose. Glucagon increases heart rate and myocardial contractility, and improves atrioventricular conduction. These effects are unchanged by the presence of beta-receptor blocking drugs. This suggests that glucagon's mechanism of action may bypass the beta-adrenergic receptor site. Because it may bypass the beta-receptor site, glucagon can be considered as an alternative therapy for profound beta-blocker intoxications. The doses of glucagon required to reverse severe beta-blockade are 50 micrograms/kg iv loading dose, followed by a continuous infusion of 1-15 mg/h, titrated to patient response. Glucagon-treated patients should be monitored for side effects of nausea, vomiting, hypokalemia, and hyperglycemia. The high cost and limited availability of glucagon may be the only factors precluding its future clinical acceptance.