Postoperative cognitive dysfunction (POCD) represents a significant clinical concern, particularly among elderly surgical patients. It is characterized by a decline in cognitive performance, affecting memory, attention, coordination, orientation, verbal fluency, and executive function. This decline in cognitive abilities leads to longer hospital stays and increased mortality. This review provides a comprehensive overview of the current progress in understanding the relevant pathogenic factors, possible pathogenic mechanisms, diagnosing, prevention and treatment of POCD, as well as suggesting future research directions. It discusses neuronal damage, susceptible genes, central cholinergic system, central nervous system (CNS) inflammation, stress response and glucocorticoids, and oxidative stress in the development of POCD, aiming to uncover the pathological mechanism and develop effective treatment strategies for POCD.