In several areas of medicine, therapeutic drug monitoring (TDM) has been proven to be a very useful tool for optimizing the therapeutic potential of various drugs and for minimizing the risk of adverse events. In pediatrics the value of TDM is generally accepted for drugs such as Theophylline and/or antiepileptics, but it is still strongly questioned for classes of drugs such as neuroleptic and tricyclic antidepressants. However, in the last 5 years evidence has been produced indicating that TDM may be a very useful tool in pediatric neuropsychiatry too. In fact, if on the one side therapeutic windows have been defined for major neuroleptics and tricyclic antidepressants, on the other side clear relationships between drug plasma concentrations and the incidence and severity of adverse reactions have been reported. Data derived from our own experience of 5 years of TDM in pediatric neuropsychiatry will be described together with data from the literature. It appears that at least for four major drugs, Haloperidol, Chlorpromazine, Imipramine, and Chlorimipramine, drug plasma levels monitoring during chronic treatment does help in a significant manner in optimizing the treatment.