It has been a concern since the 1950s that elderly patients undergoing surgery and anesthesia may suffer from postoperative cognitive changes. Because postoperative cognitive deterioration in the elderly may lead to serious medical and social consequences and is associated with increased morbidity, mortality, and high health care costs, the issue should be precisely addressed, and preventive strategies should be developed. An emerging body of evidence suggests that anesthesia and surgery have an undesirable effect on long-term cognitive function in the elderly; however, there are no convincing human data to support this correlation. Thus, the effects of anesthesia and surgery on cognition and on the natural course of underlying neurodegenerative diseases are not clear. This review presents a systemic and comprehensive clinical view of cognitive decline following anesthesia and surgery. It aims to emphasize the pathophysiological processes and risk factors of aging and potential anesthesia-and surgery-related neurodegeneration, since defining high-risk patients and preventing the problem can provide benefits for patients with neurodegenerative disease.