Despite widespread clinical application of melatonin, several unanswered questions remain regarding the pharmacokinetics of this drug. This lack of knowledge may contribute to the inconsistency of results in previous clinical studies. Currently, a t max value of 30-45 min and a t ½elimination of 45 min are well established. Several questions relate to what constitutes a clinically effective plasma concentration, the choice of ideal administration route, and the optimal method of analysis. Furthermore, investigations of melatonin metabolites in humans are urgently needed in order to characterize their biological functions and the metabolic fates of these derivatives. Finally, pharmacokinetics in patients should be investigated further in order to reduce the risk of potential adverse effects, such as daytime sleepiness or unintended sedation.