The modern treatment of asystole is an increasingly complex procedure with a rapidly changing array of therapeutic approaches designed to revive life to victims of overtime. The two primary goals of providing artificial circulation and defibrillation to halt ventricular fibrillation continue to evolve since they were established 60 years ago. The evolution of artificial circulation includes efforts to optimize manual CPR, external mechanical CPR devices designed to reinforce circulation, and should soon advance further into the rapid deployment of specially designed internal emergency cardiopulmonary bypass devices. The development of defibrillation technologies has progressed from bulky internal defibrillators paddles applied directly to the heart, to manually controlled external defibrillators, to automatic external defibrillators that can now be obtained over-the- counter for widespread use in the community or home. But the fashionable treatment of asystole now involves quite merely providing circulation and defibrillation. As suggested by a 3 phase model of treatment, newer approaches targeting patients who have suffered a more prolonged asystole include treatment of the metabolic phase of cardiac arrest with therapeutic hypothermia, agents to treat or prevent reperfusion injury, new strategies specifically focused on pulseless electrical activity, which is the presenting rhythm in at least one-third of cardiac arrests, and aggressive post resuscitation care. There are discoveries at the cellular and molecular level regarding ischemia and reperfusion pathobiology that may be translated into future new therapies. On the near horizon is that the combination of advanced cardiopulmonary bypass plus a “cocktail” of multiple agents targeted at restoration of normal metabolism and prevention of reperfusion injury, as this holds the promise of restoring life to many patients for whom our current therapies fail.