The high mortality rate of patients who initially achieve ROSC after cardiac arrest can be attributed to a unique pathophysiological process that involves multiple organs. Although prolonged whole-body ischemia initially causes global tissue and organ injury, additional damage occurs during and after reperfusion.28,29 The unique features of post–cardiac arrest pathophysiology are often superimposed on the disease or injury that caused the cardiac arrest, as well as underlying comorbidities. Therapies that focus on individual organs may compromise other injured organ systems. The 4 key components of post–cardiac arrest syndrome are (1) post–cardiac arrest brain injury, (2) post–cardiac arrest myocardial dysfunction, (3) systemic ischemia/reperfusion response, and (4) persistent precipitating pathology (Table 1). The severity of these disorders after ROSC is not uniform and will vary in individual patients based on the severity of the ischemic insult, the cause of cardiac arrest, and the patient’s prearrest state of health. If ROSC is achieved rapidly after onset of cardiac arrest, the post–cardiac arrest syndrome will not occur.