Esketamine, as the enantiomer of racemic ketamine, has garnered considerable attention in clinical practice due to its fewer side effects. In comparison with racemic ketamine, esketamine exhibits strong receptor affinity, fast onset of action, high clearance rate, and easy control effects. In recent years, it has gradually become an integral component of multimodal analgesia and has been promoted in clinical anesthesia. This review provides a comprehensive summary of the pharmacological properties, clinical applications, and side effects of esketamine, with a particular focus on its research advances and trends in various aspects including perioperative acute and chronic pain, hemodynamics, postoperative cognitive function, postoperative recovery quality, postpartum depression, pediatric anesthesia, acute brain injury, painless diagnosis and treatment, and opioid‑free anesthesia, aiming to provide a reference for the clinical application and future research of esketamine.