Neurologic injury is a potentially devastating consequence of heart surgery. Between 1% and 5% of patients undergoing cardiopulmonary bypass have postoperative strokes and 30% to 80% of patients demonstrate some neurologic dysfunction postoperatively. This review focuses on anatomic, molecular and clinical markers of neurologic injury following cardiopulmonary bypass. Attention is directed to the molecular mechanisms underlying neurologic injury and clinical biochemical markers of injury during heart surgery. Novel strategies to modulate injury are also discussed.