Human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) is having a devastating impact on African men, women and children. Antiretroviral treatment of children has lagged behind that of adults in Africa and globally. Fortunately, several national and international initiatives are helping to catalyze access of HIV-infected children to treatment. In general, the principles of antiretroviral treatment are the same for resource-rich and resource-poor settings. However, the more rapid progression of HIV disease often observed among children in Africa and some other resource-poor settings may argue for a more aggressive approach to initiation of treatment. In addition, numerous barriers to treatment of HIV-infected children in Africa and other resource-poor settings exist and must be overcome, including the expense of antiretroviral medications, lack of pediatric drug formulations, and poor human capacity and infrastructure for treatment administration. The 2.2 million African children currently living with HIV/AIDS, and many more living in poor countries on other continents, are dependent on all of us to work creatively to overcome barriers to the large-scale implementation of programs for health-restoring, life-prolonging antiretroviral treatment.