The availability and use of effective antiretroviral combination therapies has dramatically decreased the morbidity and mortality of HIV infection. Almost complete suppression of viral replication by antiretroviral therapy prevents disease progression and development of resistance, as well as leading to both regression of HIV-associated symptoms and clinically relevant immune reconstitution. More than 20 antiretroviral substances in four classes have been approved. As a result of the broad therapeutic options, HIV infection can be better treated. Although a high number of combinations can be conceived, only a small number is actually applicable. The decisions to start, monitor and change therapy have become even more difficult. The indication for treatment, the selection of the most suitable therapy for an individual, the counseling of the patient, and the monitoring of the success of treatment demand a high level of knowledge and experience. Virologic failures of modern antiretroviral therapy regimens are rare in adherent patients.