Neurologic injury is a common complication of major cardiovascular procedures including coronary artery bypass graft (CABG) surgery, coronary valve replacement, and aortic aneurysm surgery. However, despite ongoing research in the field of neuroprotection, there are currently few pharmacologic and interventional options to effectively protect the brain and spinal cord in the postoperative period. CSF drainage after aortic surgery currently stands as the only neuroprotective intervention that has been consistently shown to protect the spinal cord from ischemic injury, leading to significantly fewer patients with paraplegia and paraparesis. There is promising but conflicting evidence about the potential benefits of agents such as dexmedetomidine, lidocaine, magnesium, and erythropoietin in preventing postoperative stroke and cognitive dysfunction. Postoperative hypothermia has also been studied in preventing neurologic injury after cardiopulmonary bypass. With the rate of cardiovascular surgeries increasing yearly, further investigations are needed to validate many of these therapies and discover new ways to protect the brain and spinal cord from intraoperative and postoperative injuries in this high-risk population.