Neurological injury is a devastating complication of cardiac surgery that results in a longer duration of hospitalization, increased costs, and increased likelihood of death. Such injury can affect any level of the central nervous system, and its manifestations are broad, ranging from neurocognitive dysfunction to frank stroke. Many variables have been found to be indicative or risk for perioperative neurological injury, but the predictive models are more useful for stroke risk than for neurocognitive dysfunction. Strategies aimed at reducing neurological injury during cardiac surgery have focused, for the most part, on the technical aspects of cardiopulmonary bypass. The concomitant performance of carotid endarterectomy and cardiac surgery continues to be controversial, although the management of patients with symptomatic carotid stenosis is better defined. Cerebral embolism, including atheroembolism from the ascending aorta, has an important role in the pathogenesis of neurological injury of all types. Epiaortic ultrasound imaging of the aorta is a sensitive technique for the identification of atherosclerosis of the ascending aorta at the time of surgery, which can allow it to be avoided and therefore reduce the risk for atheroembolism. Results of laboratory investigations have provided insight into the mechanisms of ischemic neuronal injury and a basis for the development of neuroprotective drugs. Neuroprotection may best be accomplished during cardiac surgery because, in contrast to nonsurgical situations, potential agents can be administered before the neurological insult occurs. Reducing the incidence of perioperative stroke will require a multidisciplinary approach that includes novel diagnostic and therapeutic strategies.