Background: delirium is an extremely common syndrome in the intensive care unit (ICU). It is characterized by acute fluctuations and alterations in attention and arousal. Critically ill patients are at particularly high risk, and those that develop delirium are more likely to experience poor clinical outcomes such as prolonged duration of ICU and hospital length of stay, and increased mortality. Melatonin and melatonin agonists (MMA) have the potential to decrease the incidence and severity of delirium Aim of the study: to review and assess the role of melatonin in several clinical applications in perioperative management, critical care and pain medicine. Conclusion: melatonin reported eight peri-operative outcomes: anxiety; analgesia; sleep quality; oxidative stress; emergence behavior; anesthetic requirements; steal induction; and safety. Evidence-based, multi modal, surgical and anesthetic approaches have reduced morbidity and mortality following surgical procedures.