The natural course of mostly perinatally acquired childhood HIV infection shows some special characteristics. Compared to adults the initial viral load is higher, persists for a longer period of time and without antiretroviral therapy up to 20% of infected children develop AIDS within the first year of life. It is therefore desirable to stop disease progression before an irreversible deterioration of the immune system has occurred by initiating early antiretroviral therapy. The choice of antiretroviral agents is difficult because data from adult studies cannot be directly applied to infants and data on antiretroviral therapy in pediatric patients are limited. The current national and international guidelines for antiretroviral therapy in perinatally acquired HIV infection are discussed.