Combination anti-retroviral treatment (cART) has been highly successful in preventing mother to child transmission of HIV and in reducing mortality and morbidity in HIV infected children. cART is now recommended for all HIV infected infants and selected older children. These children will need to take cART until adulthood so the aim is to use cART with low risks of virological failure, resistance and toxicity. Increasing numbers of antiretroviral drugs are becoming available for children. Ongoing studies are needed to determine the correct doses for children, improve adherence and to assess potential toxicity and drug interactions (such as between ritonavir and inhaled fluticasone).