Melatonin possesses sedative, hypnotic, analgesic, antiinflammatory, antioxidative, and chronobiotic properties that distinguish it as an attractive alternative premedicant. A qualitative systematic review of the literature concerning the perioperative use of melatonin as an anxiolytic or analgesic in adult patients was carried out using the recommended guidelines provided by the Cochrane Handbook for Systematic Reviews of Interventions. Nine of the 10 studies showed statistically significant reduction of preoperative anxiety with melatonin premedication compared with placebo. An opioid-sparing effect or reduced pain scores were evident in five studies whereas three studies were contradictory. Thus, melatonin premedication is effective in ameliorating preoperative anxiety in adults, but its analgesic effects remain controversial in the perioperative period. Additional well designed randomized controlled trials are necessary to compare melatonin premedication with other pharmacological interventions, investigate its effect on more varied surgical populations, and to delineate its optimal dosing regimen.