Resistance to antiretroviral drugs is one of the major pitfalls of combined treatment of HIV infection. Thus, timely identification of drug resistant HIV strains and precise evaluation of the level of resistance to the different antiretroviral drugs are crucial in the management of treated patients. Phenotypic determination of antiretroviral drug resistance evaluates the ability of an HIV strain to replicate in the presence of drug(s). Thus, this assay (either conventional or recombinant) provides a direct estimate of drug susceptibility. However, it is relatively difficult to perform and requires dedicated facilities. Thus, its use is still restricted. Genotypic determination of drug resistance is based upon detection of specific mutations in HIV genes encoding target enzymes or receptors. The assay provides an indirect evidence of drug susceptibility. However, it is easy to perform and does not require dedicated facilities. Thus, it is widely utilized in clinical practice. Its major limitation concerns the complexity of results interpretation which still awaits a general consensus.