This article outlines interventions used to improve outcomes for patients with hypoxic-ischemic brain injury after cardiac arrest. Emergent management of patients after cardiac arrest requires prevention and treatment of primary and secondary brain injury. Primary brain injury is minimized by excellent initial resuscitative efforts. Secondary brain injury prevention requires the detection and correction of many pathophysiologic processes that may develop in the hours to days after the initial arrest. Key physiologic parameters important to secondary brain injury prevention include optimization of mean arterial pressure, cerebral perfusion, oxygenation and ventilation, intracranial pressure, temperature, and cortical hyperexcitability. This article outlines recent data regarding the treatment and prevention of secondary brain injury. Different patients likely benefit from different treatment strategies, so an individualized approach to treatment and prevention of secondary brain injury is advisable. Clinicians must use multimodal sources of data to prognosticate outcomes after cardiac arrest while recognizing that all prognostic tools have shortcomings. Neurologists should be involved in the postarrest care of patients with hypoxic-ischemic brain injury to improve their outcomes. Postarrest care requires nuanced and patient-centered approaches to the prevention and treatment of primary and secondary brain injury and neuroprognostication.