The post-cardiac arrest syndrome is a delicate, critical and complex condition that involves most patients resuscitated by a cardiac arrest. The main pathophysiological mechanism of this syndrome is a widespread ischemia-reperfusion damage, then there are other pathological alterations involving various organs which, if untreated, can evolve into multiorgan dysfunction. For this reason, a series of diagnostic-therapeutic actions (bundles) are necessary to ensure a correct management of the post-cardiac arrest syndrome: adequate oxygenation and ventilation, hemodynamic stabilization, temperature control, early prediction of neurological outcome, optimization of metabolic aspects, indication and timing of coronary angiography. The management of the post-cardiac arrest syndrome, the fifth link in the chain of survival, consists of a set of early, complex and multidisciplinary interventions, which must be promptly started, immediately after a return of spontaneous circulation, regardless of the location of cardiac arrest presentation, and it aims to obtain a good hemodynamic and neurological recovery. In this review, we will address the most recent scientific recommendations in the various areas of management of post-cardiac arrest syndrome that have led in recent years to a change in the practical approach to the comatose patient after cardiac arrest.