This chapter reviews the pathophysiology, common clinical syndromes, ancillary investigations, prognosis, and medical management of Hypoxic-ischemic brain injury (HI-BI). Long-term impairment of consciousness is a major cause of neurological disability and represents the main cause of withdrawal of life-support in patients with HI-BI. Seizure-like activity may occur in the context of HI-BI and typically begins within 24 hours following cardiac arrest. Movement disorders may occur acutely, but more typically develop in a delayed fashion, months to years following onset of HI-BI. Cognitive impairment occurs in almost half of survivors at 1 year following resuscitation from HI-BI due to cardiac arrest. Therapeutic hypothermia may affect neurological prognostic signs following cardiac arrest. Hypothermia may also decrease clearance of concomitant paralytic and sedative drugs. In one study utilizing continuous amplitude integrated EEG, electrocerebral silence, following rewarming after therapeutic hypothermia, had a high specificity for poor outcome.