Therapeutic drug monitoring has the promise to become a part of routine patient care in the treatment of HIV infection. It is known that plasma drug concentrations of protease inhibitors and non-nucleoside reverse transcriptase inhibitors are better predictors of antiviral response or toxicity than drug dose is. Furthermore, high interpatient variability is significant. In addition, therapeutic drug monitoring may be used as a direct and objective instrument to measure non-adherence. This review describes possibilities and limitations of therapeutic drug monitoring in HIV treatment.