The pediatric highly-active antiretroviral therapy (HAART) has shown enormous progress in recent years but still, a high percentage of children continue to experience treatment failure. The main causes found responsible are the development of drug resistance, inadequate dosing and poor adherence. This review is aimed at exploring the current status of antiretroviral therapy in children with focus on the interaction between disease, drug and patient behavior, all of which are strongly correlated .An overview of HIV viral characteristics and of the available antiretroviral drug classes currently combined to avoid development of resistance has been also discussed.