Cerebral dysfunction and injury in the ICU presents as focal neurologic deficits, seizures, coma, and delirium. These syndromes may result from a primary brain insult, such as stroke or trauma, but commonly are a complication of a systemic insult, such as cardiac arrest, hypoxemia, sepsis, metabolic derangements, and pharmacologic exposures. Many survivors of critical illness have cognitive impairment, which is believed to underlie the poor long-term functional status and quality of life observed in many critical illness survivors. Although progress has been made in characterizing the epidemiology of cerebral dysfunction in the ICU, more research is needed to elucidate underlying mechanisms that might represent targets for therapeutic intervention.