The concept of managing pharmacotherapy based on plasma drug concentrations has been used for decades in a variety of clinical settings. The interest in therapeutic drug monitoring (TDM) of antiretroviral drugs has grown significantly since highly active antiretroviral therapy (HAART) became a standard of care in clinical practice. A primary characteristic of TDM of antiretroviral drugs is that multiple agents are concomitantly used in HAART regimens. Inadequate drug concentrations may lead to evolution of drug resistance mutations and endanger present and future treatment options. A number of clinical trials have demonstrated that drug serum concentrations are an important factor in response to therapy for HIV, but whether TDM will become a tool for the routine management of HIV infection remains to be determined. This review includes an illustrative case report of measuring concentrations of antiretroviral drugs in a pediatric patient.