International guidelines do not recommend therapeutic drug monitoring (TDM) of HIV-infected children as a routine measurement as part of medical management. There are, however, several clinical scenarios in which TDM may be indicated. Underdosing may be one of the major risks, especially in younger children. No randomized controlled clinical trials have been conducted to assess the added value of TDM in HIV-infected children, making recommendations for TDM in children with HIV/AIDS merely based on expert opinion. There is a need for more descriptive studies on the usefulness of TDM in HIV-infected children to convince pediatricians worldwide to let more children benefit from TDM.