In order to adapt African programs for antiretroviral treatment (ART) to childrens needs, a good understanding of the unique features of pediatric HIV in Africa and realistic expectations of the results of such programs are crucial. We compared pediatric HIV in African settings to pediatric HIV in Western settings and to adult HIV in African settings. As an illustration, we also compared baseline characteristics and ART-outcomes from 15 African pediatric studies, 11 Western pediatric studies and 15 studies of African adults. Several differences in diagnostic, clinical, immunological and virological characteristics were identified, as well as variations in the most influential factors for disease progression and response to ART. Environmental factors may influence disease progression, mortality, loss to follow-up, adherence and the need to adapt the regimen. Many of the responses to ART are two-phased, the first phase taking longer in children than in adults. The selected African pediatric programs recorded a higher increase in median CD4-percent than the selected Western pediatric programs and a higher increase in CD4-count than the selected African adult programs. Compared to the adult programs, the African pediatric programs had lower drop-out rates, higher reported adherence levels and comparable mortality rates. The Western pediatric programs, however, had the lowest mortality rates. While several challenges complicate comparisons between ART-programs, increased knowledge of the unique features of pediatric HIV in Africa may greatly assist in improving pediatric HIV care on a global level.