The recent studies focusing on the pharmacokinetics of tramadol in children contributed to the increase popularity of tramadol as an analgesic alternative in clinical practice. Tramadol is a racemic mixture of 2 enantiomers that have comparable pharmacokinetic profile and this lack of difference is also observed with their main active metabolite, O-demethyl tramadol (M1). The serum concentrations of this metabolite depend largely on the activity of the cytochrome P450 and particularly of the enzyme CYP2D6 which reaches its maturity in the newborn. Nevertheless, the interindividual variability observed in the pharmacokinetics of tramadol and consequently in the pharmacodynamic profile is mainly due to the genetic polymorphism of cytochrome P450.