The post-cardiac arrest syndrome is a highly inflammatory state characterized by organ dysfunction, systemic ischemia and reperfusion injury, and persistent precipitating pathology. Early critical care should focus on identifying and treating arrest etiology and minimizing further injury to the brain and other organs by optimizing perfusion, oxygenation, ventilation, and temperature. Patients should be treated with targeted temperature management, although the exact temperature goal is not clear. No earlier than 72 hours after rewarming, prognostication using a multimodal approach should inform discussions with families regarding likely neurologic outcome.