Human immunodeficiency virus (HIV) infection is one of the most prominent health care challenges world wide. In Western industrialized countries where common access to antiretroviral drugs exists, HIV infection is a well treatable disease in the long-term for most patients. However, given the possible evolution of drug-resistance, the right combination of antiretroviral drugs in first-line therapy is crucial for maintaining long-term success. For each individual patient, the ideal time to start antiretroviral therapy must be carefully selected. The individual risk of progression to acquired immunodeficiency syndrome (AIDS) on the one hand, and the risks of long-term toxicity and adherence problems under therapy on the other hand must be taken into account. Each patient should be counseled according to present treatment guidelines on when and how to start HAART, taking into account the surrogate markers CD4-cell count and HIV-RNA as well as clinically apparent HIV-associated disease.