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Out-of-hospital cardiac arrest (OHCA) is a major public health problem. In the United States, OHCA accounts for more premature deaths than any other cause. For over a half-century, the national “Guidelines” for resuscitation have recommended the same initial treatment of primary and secondary cardiac arrests. Using this approach, the overall survival of patients with OHCA, while quite variable, was generally very poor. One reason is that the etiologies of cardiac arrests are not all the same. The vast majority of nontraumatic OHCA in adults are due to a “primary” cardiac arrest, rather than secondary to respiratory arrest. Decades of research and ongoing reviews of the literature led the University of Arizona Sarver Heart Center Resuscitation Research Group to conclude in 2003 that the national guidelines for patients with primary cardiac arrest were not optimal. Therefore, we instituted a new, non-guidelines approach to the therapy of primary cardiac arrest that dramatically improved survival. We called this approach cardiocerebral resuscitation (CCR), as it is the heart and the brain that are the most vulnerable and therefore need to be the focus of resuscitation efforts for these patients. In contrast, cardiopulmonary resuscitation should be reserved for respiratory arrests. Cardiocerebral resuscitation evolved into 3 components: the community, with emphasis for lay individuals to “Check, Call, Compress” and use an automated external defibrillator if available; the Emergency Medical Services, that emphasizes delayed intubation in favor of passive ventilation, urgent and near continuous chest compressions before and immediately after a single indicated shock, and the early administration of epinephrine; and the third component, added in 2007, the designations of hospitals in Arizona that request this designation and agree to receive patients with return of spontaneous circulation following OHCA and to institute state-of-the-art postresuscitation care that includes urgent therapeutic mild hypothermia and cardiac catheterization as a Cardiac Receiving Center. Each component of CCR is critical for optimal survival of patients with primary OHCA. In each city, county, and state where CCR was instituted, the result was a marked increase in survival of the subgroup of patients with OHCA most likely to survive, for example, those with a shockable rhythm. The purpose of this invited article on CCR is to review this alternative approach to resuscitation of patients with primary cardiac arrest and to encourage its adoption worldwide so that more lives can be saved.