Background: Sub-Saharan Africa has the largest burden of pediatric HIV in the world. Global target has been set for eradication of pediatric HIV by 2015 but there are still so many complex issues facing HIV infected and affected children in the sub-continent. Objective: To review the current and emerging challenges facing pediatric HIV care in sub-Saharan Africa; and proffer solutions that could help in tackling these challenges. Method: A Medline literature search of recent publications was performed to identify articles on “pediatric HIV”, “HIV and children”, “HIV and infants”, “HIV and adolescents” in sub-Saharan Africa. Result: There are a number of challenges and emerging complex issues facing children infected and affected by HIV in sub-Saharan Africa. These include late presentation, limited access to pediatric HIV services, delayed diagnosis, infant feeding choices, malnutrition, limited and complex drug regimen, disclosure, treatment failure and reproductive health concerns. A holistic cost effective preventive, diagnostic and treatment strategies are required in order to eliminate pediatric HIV in SSA. Conclusion: HIV infected children and their families in sub-Saharan Africa face myriad of complex medical and psychosocial issues. A holistic health promotional approach is being advocated as the required step for eradication of pediatric HIV in Africa.