Esketamine is an antagonist of the N-methyl-D-aspartate (NMDA) receptor and exerts antianxiety, hypnotic, sedative, and analgesic effects by interacting with NMDA receptors, opioid receptors, M-choline receptors, monoamine receptors, adenosine receptors, and other purine receptors. As the more potents isomer of ketamine, it is about twice as potent as ketamine. Compared with ketamine, esketamine has the characteristics of rapid onset and metabolism, strong analgesia, slight respiratory depression, rapid recovery of cognitive function, and low incidence of psychiatric side effects. It has become a new choice of pediatric anesthesia drugs. This article reviews the pharmacological properties of esketamine and its recent application in pediatric anesthesia, and provides reference for the safe use of esketamine in pediatric perioperative period.