Several relationships have been reported between antiretroviral drug concentrations and the efficacy of treatment, and toxicity. Therefore, therapeutic drug monitoring (TDM) may be a valuable tool in improving the treatment of HIV-1-infected patients in daily practice. In this regard, several measures of exposure have been studied, e.g. trough and maximum concentrations, concentration ratios and the inhibitory quotient. However, it has not been unambiguously established which pharmacokinetic parameter should be monitored to maintain optimal viral suppression. Each pharmacokinetic parameter has its pros and cons. Many factors can affect the pharmacokinetics of antiretroviral agents, resulting in variability in plasma concentrations between and within patients. Therefore, plasma concentrations should be considered on several occasions. In addition, the interpretation of the drug concentration of a patient should be performed on an individual basis, taking into account the clinical condition of the patient. Important factors herewith are viral load, immunology, occurrence of adverse events, resistance pattern and comedication. In spite of the described constraints, the aim of this review is to provide a practical guide for TDM of antiretroviral agents. This article outlines pharmacokinetic target values for the HIV protease inhibitors amprenavir, atazanavir, indinavir, lopinavir, nelfinavir, ritonavir and saquinavir, and the non-nucleoside reverse transcriptase inhibitors efavirenz and nevirapine. Detailed advice is provided on how to interpret the results of TDM of these drugs.