Syndromes of global cerebral dysfunction that are associated with critical illness include acute disorders (eg, coma, delirium) and chronic processes (ie, cognitive impairment). These syndromes can result from direct cerebral injury; however, many cases develop as a complication of a systemic insult. Coma frequently evolves into phenomenologically distinct disorders of consciousness; it must be differentiated from conditions in which consciousness is preserved, as in the locked-in state. Advances have been made in defining, scoring, and delineating the epidemiology of cerebral dysfunction in the ICU, but research is needed to elucidate underlying mechanisms, with the goal of identifying targets for prevention and therapy.