Critical illness frequently is associated with neurologic failure that may involve the central and peripheral nervous systems. Central nervous system failure is associated with a spectrum of neurobehavioral changes including delirium, coma, and long-term cognitive dysfunction. Peripheral neurologic failure, or critical illness neuromuscular abnormalities, is suggested by diffuse arreflexic weakness and protracted respiratory insufficiency, and may also persist long after the acute hospitalization. While the burden of neurological disease complicating critical illness is considerable, preventive or therapeutic options are limited. This article provides an overview of research evaluating the relationship between critical illness and neurologic function, with a special emphasis on underlying mechanisms.