This review assesses the role of epinephrine in cardiopulmonary resuscitation from the perspective of mechanisms of action, cardiac and cerebral effects, and use in human beings. We reviewed the literature from 1966 onward, using a Medline Search of the National Library of Medicine with the key words: "heart arrest," "resuscitation," and "epinephrine." Pertinent articles that represented original research were critically appraised by at least two authors. We concluded that the Advanced Cardiac Life Support recommended dose of epinephrine (1 mg or 0.007 to 0.014 mg/kg) has little scientific basis. Evidence from animal studies demonstrates that doses of 0.1 to 0.2 mg/kg are required to significantly improve myocardial and cerebral blood flow and resuscitation rates. Limited human data confirm the dose-dependent vasopressor response to epinephrine and the potential for improved immediate survival with higher doses. We suggest that randomized controlled human trials are needed to document the usefulness of higher doses of epinephrine in cardiopulmonary resuscitation.