Out-of-hospital resuscitation protocols for patients suffering cardiac arrest have historically included cardiopulmonary resuscitation, defibrillation, and rapid transport to a hospital. For many years, use of drugs to improve myocardial perfusion or to correct arrhythmias that occur during cardiac arrest has been part of prehospital efforts to revive patients in ventricular tachycardia or ventricular fibrillation. Use of some of these drugs, however, may be based more on tradition than on well-documented evidence of efficacy. The authors reviewed pertinent data on the vasopressors epinephrine and vasopressin and the antiarrhythmics amiodarone and lidocaine to evaluate the usefulness of these drugs in cardiac arrest. They found little clinical data supporting the prehospital use of lidocaine in cardiac arrest, and despite a great deal of laboratory and clinical data addressing the efficacy of epinephrine, there is no large, randomized, controlled clinical trial supporting its use. Data on amiodarone and vasopressin support the use of these drugs in out-of-hospital resuscitation efforts.