In this paper we present an overview on the use of TDM in the treatment of HIV-1-infected children. The processes of growth and development have a significant impact on drug metabolism. The use of TDM makes it possible to optimize plasma drug concentrations of antiretroviral drugs. This is important when one considers that the levels of viral suppression and drug toxicity in adults and children are associated with the plasma concentration of PIs and NNRTIs. Indeed, in clinical practice the use of TDM in the treatment of HIV-1-infected children has favorable results. However, there is a serious shortage of population reference values of antiretroviral medication in children. Targeting plasma drug levels in children to adult reference values may be insufficient because of the unique features of HIV infection in children. Apart from its primary function for dose optimization, TDM can also be used as a tool to assess adherence to antiviral medication. One should, however, be cautious to base assumptions on plasma levels alone because aberrant plasma levels may also be the result of other factors such as changes in nutritional habits, drug-drug interactions, or changing gastric motility. We conclude that TDM is a useful tool in the treatment of HIV-1-infected children. Additional data are needed to establish child-specific reference values and to assess the optimal method of TDM.