Ketamine is a racemic mixture: Dextrorotatory esketamine is four times more active as a non-competitive N-methyl-D-asparate receptor antagonist than levorotatory arketamine, and twice as potent as analgesic and anesthetic as the racemate. At equipotent dose, esketamine improves postoperative awakening and neurocognitive impairment with less unpleasant psychic effects. Experimentally, esketamine exerts less unwanted effects on cardiacCardiac functions and preconditioning. Ketamine induces neuro- and astroglial plasticity and activates neurogenesis in animals. Only esketamine induces neuroregeneration. In acute intracranial pathologies, ketamine reduces harmful depolarizations. Perioperative esketamine offers better hemodynamic stability and postoperative recovery with less pain, opioid need, respiratory depression, gastrointestinal dysfunction, sleep disturbance, and inflammation. In children, esketamine can provide calmer awakening after sevoflurane, and in the elderly earlier mobilization and better rehabilitation. Racemic and es-ketamine can reduce postoperative neurocognitive disorder and/or delirium. Studies show additional value for prophylaxis and treatment of perioperative depression in cancerCancer surgery and Caesarean section. Racemic and es-ketamine are efficient antinociceptive components in opioid-sparing and opioid-free anesthesia, with advantages in obesity, respiratory handicap, and obstructive sleep apnea. Esketamine’s most significant benefits include better perioperative analgesia and anesthesia at half-dose racemic ketamine, and less unwanted brain impact.