Critical illness can and often does lead to significant cognitive impairment and to the development of psychological disorders. These conditions are persistent and, although they improve with time, often fail to completely abate. Although the functional correlates of cognitive and psychological morbidity (depression, anxiety, and posttraumatic stress disorder) have been studied, they may include poor quality of life, inability to return to work or to work at previously established levels, and inability to function effectively in emotional and interpersonal domains. The potential etiologies of cognitive impairment and psychological morbidity in ICU survivors are particularly poorly understood and may vary widely across patients. Potential contributors may include the potentially toxic effects of sedatives and narcotics, delirium, hypoxia, glucose dysregulation, metabolic derangements, and inflammation. Patients with preexisting vulnerabilities, including predisposing genetic factors, and frail elderly populations may be at particular risk for emergence of acceleration of conditions such as mild cognitive impairment.