When immediate defibrillation fails, successful cardiac resuscitation is contingent on prompt reestablishment of myocardial blood flow. Conventional methods of closed-chest resuscitation generates only critical levels of myocardial blood flow and therefore are of limited value for successful resuscitation. Methods that optimize the site, depth, rate and duration of precordial compression may increase myocardial blood flow, however, the lack of objective measurements of their hemodynamic effects limits the optimal performance of this resuscitation method. With the recognition that elimination of CO2 is flow limited, measurement of end-expired PCO2 has emerged as a practical option for continuous assessment of systemic blood flow and coronary perfusion pressure. With measurement of the end-expired PCO2, operator fatigue may be recognized, the technique of precordial compression may be optimized, and the likelihood of restoring spontaneous circulation may be estimated. When conventional cardiac resuscitation fails or is predicted to fail by measurements of end-tidal PCO2, more effective interventions such as open-chest direct cardiac massage may be instituted. Regarding the vast resuscitation polypharmacy, only agents that act by selectively augmenting coronary perfusion pressure and myocardial blood flow are of proven benefit for successful resuscitation.