Today, initial treatment of an HIV infection usually leads to a prolonged suppression of viral replication, and to an improvement in the prognosis. However, the number of patients in whom such treatment is not, or not lastingly, successful is constantly increasing. Salvage therapy, that is, therapy employed after initial therapy failure, has a good chance of revitalizing success. If several combination therapies have failed, treatment is considerably more difficult, in particular when multiple resistances to all antiretroviral subclasses have developed. Available options in such a case are intensive salvage therapy with multi-drug regimens, partially effective treatment or interruption of treatment. The aim of antiretroviral therapy must therefore be to prevent therapy failures or to delay them for as long as possible. Cohort studies offering an opportunity to select good candidates for such long-term therapeutic strategies are currently ongoing.