An array of clinical events may lead to perioperative neurological injury. We first review the general cellular mechanisms leading to brain tissue injury and death. The genesis and mechanisms of injury after cerebral aneurysm surgery, traumatic brain injury, postoperative vascular insult in patients with severe cerebrovascular disease are discussed, as are strategies for prevention and treatment. More has become known about the epidemiology, risk factors and potential preventive strategies in postoperative delirium, and, to a lesser extent, postoperative cognitive dysfunction. Finally, emerging concepts in clinical brain protection are discussed, including preconditioning, gene therapy and stem cells.