Basic life support and rapid defibrillation for ventricular fibrillation or pulseless ventricular tachycardia are the only two interventions that have been shown unequivocally to improve survival after cardiac arrest. Several drugs are advocated to treat cardiac arrest, but despite very encouraging animal data, no drug has been reliably proven to increase survival to hospital discharge after cardiac arrest. This review focuses on recent experimental and clinical data concerning the use of vasopressin, amiodarone, magnesium, and fibrinolytics during advanced life support (ALS). Animal data indicate that, in comparison with epinephrine (adrenaline), vasopressin produces better vital organ blood flow during cardiopulmonary resuscitation (CPR). These apparent advantages have yet to be converted into improved survival in large-scale trials of cardiac arrest in humans. Data from two prospective, randomized trials suggest that amiodarone may improve short-term survival after out-of-hospital ventricular fibrillation cardiac arrest. On the basis of anecdotal data, magnesium is recommended therapy for torsades de pointes and for shock-resistant ventricular fibrillation associated with hypomagnesemia. In the past, CPR has been a contraindication to giving fibrinolytics, but several studies have demonstrated the relative safety of fibrinolysis during and after CPR. Fibrinolytics are likely to be beneficial when cardiac arrest is associated with plaque rupture and fresh coronary thrombus or massive pulmonary embolism. Fibrinolysis may also improve cerebral microcirculatory perfusion once a spontaneous circulation has been restored. A planned, prospective, randomized trial may help to define the role of fibrinolysis during out-of-hospital CPR.