Both short- and long-term cognitive changes continue to occur after coronary artery bypass grafting (CABG), but the pathophysiology of these neurobehavioral changes remains incompletely understood. The persistence of mild postoperative neurocognitive changes despite multiple improvements in the cardiopulmonary bypass procedure may be partially because of surgical populations being older and having more prevalent comorbid disease. The cause of the early postoperative changes is most likely multifactorial and may include ischemic injury from microemboli, hypoperfusion, and other factors resulting from major surgery. Several lines of evidence suggest that the late cognitive decline between 1 and 5 years after surgery may be secondary to high rates of cerebrovascular disease among candidates for CABG. A history of hypertension and other risk factors for vascular disease is known to be associated with increased risk for long-term cognitive decline in community-dwelling elderly individuals. Cerebrovascular risk factors are also associated with silent magnetic resonance imaging abnormalities in patients undergoing CABG. Thus, whereas both short- and long-term postoperative cognitive changes have been associated with CABG, only the short-term, transient changes appear to be directly related to the use of cardiopulmonary bypass.