Postoperative depression (PD) is a kind of postoperative mental disorder caused by various factors which is characterized by a significant and persistent depressive state. Esketamine is an intravenous anesthetic drug with rapid antidepressant effect, but there are still few studies in the field of PD. This article explains the mechanism of action of esketamine in preventing PD, summarizes the study on the effect of esketamine on PD in patients during perioperative period, proposes recommendations for the perioperative use of esketamine, aiming to provides reference for the application and scientific research of esketamine in China.