The interest in therapeutic drug monitoring (TDM) of antiretroviral drugs is growing rapidly. For the protease inhibitors, and to a lesser extent for the non-nucleoside reverse transcriptase inhibitors, relationships between plasma drug concentrations and their efficacy and toxicity have been identified. Furthermore, the pharmacokinetics of especially the protease inhibitors vary widely between patients, suggesting a role for TDM to individualize antiretroviral therapy. Recently, randomized, prospective clinical trials evaluating the role of TDM in the management of HIV-1-infected patients showed promising results. However, there are still many questions to be answered before large-scale introduction of TDM can be justified (e.g., which pharmacokinetic parameter should be optimized, and what is the minimal effective concentration). This review summarizes the basis for TDM of antiretroviral drugs and discusses the problems and prospects of this potential tool in the care for HIV-1-infected individuals.