In the last few years the antiretroviral combination therapy has drastically reduced the mortality and morbidity in HIV-infected patients. The aim of this treatment is the suppression of viral replication by a combination of at least three active drugs. However, about 20-40% of the patients experience a virological treatment failure, mostly due to development of drug resistant viruses on the background of insufficient drug levels. This resistances can be detected geno- and phenotypically by validated techniques. In the individual case of treatment failure resistance testing and therapeutic drug monitoring can help to find the most appropriate drug combination in the right dosage.