Therapeutic Drug Monitoring (TDM) became these last years very attractive in clinical and fundamental researches for several reasons. In one hand, 21 antiretroviral drugs are currently used and pharmacological studies to understand drugs interactions and to choose the best drug combinations are needed. On the other hand, we observe treatment failure and numerous side effects such as lipodystropy in HIV treated patients. An inadequate intracellular concentration of the drug might be one of the main raisons of the ineffectiveness of therapy. Moreover, beside interindividual metabolism variations, unique posologies are still prescribed. Clinical trial uses a necessary statistic method, but it leads to one dose which should fit all subjects.We discuss here the importance ofTDM using both plasmatic and intracellular analyses to improve our antiretroviral drug understanding and try to lead to the personalization of treatment.