Cerebral injury after cardiac surgery is still a major cause of mortality and morbidity after cardiac surgery. In an aging patient population the incidence is likely to increase. Comparisons between cardiac and other major surgery suggested that cardiopulmonary bypass (CPB) causes the neurological sequelae. Strategies to avoid brain injury target the reduction of emboli floating in the cerebral circulation, adequacy of cerebral oxygenation, and minimization of the whole body inflammatory response to the bypass circuit. Experimental and clinical studies demonstrated that manipulation of CPB can reduce abundant cerebral blood flow and the embolic load to the brain. Hematocrit, temperature, blood pressure, and acid-base status during CPB are parameters that have impact on the neurological outcome and can be optimized. Other possibilities to avoid cerebral complications include improvements of surgical techniques and devices or the application of new therapeutic drugs. However, further experimental studies and, most importantly, prospective randomized clinical trials are warranted to prove new innovative concepts in clinical practice.