Antiretroviral treatments have transformed the prognosis for patients with HIV infection. However, because the treatment is only virostatic and has substantial side effects, especially in the long term, it should not be proposed to all HIV-infected patients but only to symptomatic patients or asymptomatic patients with immune deficiency (CD4 cell count < 350/mm3). The aim of antiretrovirals is to lower the viral load to undetectable levels for prolonged periods and thus enable immune reconstitution and prevent selection of resistant mutants. In initiating treatment, the preferred options are a combination of 2 HIV nucleoside reverse transcriptase inhibitors associated with either a non-nucleoside reverse transcriptase inhibitor or a protease inhibitor, the latter with a low dose of ritonavir. Optimal compliance is the key to successful treatment and requires that the aims of the antiretroviral therapy be clearly explained to the patient. Treatment failure usually occurs in two types of situations. Failure after an initial regimen is often related to poor compliance and sometimes to interactions between drugs. Conversely, in patients for whom several regimens have failed, the accumulation of resistant mutations compromises the antiretroviral activity. Genotype resistance tests help in the choice of a new treatment regimen that should ideally include at least 2 active molecules. In these situations the new antiviral drugs with novel mechanisms of action, such as the entrance inhibitors, are clearly of interest.