Abstract:Postoperative delirium (POD) is a common complication in elderly patients after surgery, significantly affecting prognosis and increasing mortality rates. The underlying mechanisms of POD remain unclear, with diverse risk factors making prevention difficult and treatment outcomes unsatisfactory. Esketamine is a high-affinity N-methyl-D-aspartate (NMDA) receptor antagonist known for its anesthetic and analgesic properties. Besides its widespread use in perioperative anesthesia and pain management, esketamine has shown promising clinical applications across various disciplines including psychiatry and critical care. This review summarizes recent advances and mechanisms of esketamine in preventing and treating POD, offering new insights for clinical practice.