HIV drug resistance can be defined as any change (in protease, reverse transcriptase gene or envelope protein) that improves viral replication in the presence of an inhibitor. One of the most important causes of treatment failure is the development of resistance to antiretrovirals by HIV. Resistance studies have highlighted distinct evolution patterns of mutations and cross resistance among drug classes, which have the ability to impact on the choice of subsequent salvage treatment. A number of resistance testing technologies have been developed to measure HIV drug resistance and prospective studies have shown that the use of these resistance tests have the ability to improve the virological response to a salvage regimen. These tests are now widely used in developed countries and are recommended in case of therapeutic failure in treated patients and in case of recent infection in naive patients.