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Extracorporeal cardiopulmonary resuscitation (ECPR) is recommended for the treatment of refractory cardiac arrest when spontaneous circulation activity fails to resume despite optimal conventional cardiopulmonary resuscitation throughout the chain of survival. The aim of this second line of treatment is to restore adequate organ perfusion, especially to the brain, by compensating for the patient’s circulatory and respiratory failure while the cause of the cardiac arrest is identified and treated. As summarized by international guidelines, ECPR should be delivered by specialized teams, for carefully selected patients, and within a strict timeframe to improve the probability of neurologically intact survival. The anticipation of a pre-hospital and then in-hospital care pathway, along with coordinated multidisciplinary management, is essential for optimal patient care. The objective of this review is to describe the current data on ECPR as a treatment for refractory cardiac arrest, with a focus on the findings from randomized studies on ECPR for out-of-hospital cardiac arrest—despite their limited number and varying methodologies—while outlining which patients should be treated with ECPR, as well as when and how ECPR should be implemented to increase the probability of neurologically intact survival.