Esketamine, which was recently introduced in China, is a type of intravenous general anesthetic that is widely used in clinical practice for general anesthesia and anti-depression therapy. Studies have found that esketamine can be safely used to intrathecally produce analgesic, sedative, and anti-depressive effects at subanesthetic doses. This review summarizes the mechanism of action, safety, adverse reactions, and various clinical applications of esketamine intrathecally, so as to provide relevant references for further research.