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To assess the importance of anemia in HIV-infected children in western and tropical settings.A systematic review with a descriptive component.Four databases were searched and reference lists of pertinent articles were checked. Studies that reported data on anemia or hemoglobin levels in HIV-infected children were selected and grouped according to the location and the definition of anemia.Thirty-six studies met the inclusion criteria. Mild (hemoglobin <11 g/dl) and moderate (hemoglobin <9 g/dl) anemia were more prevalent with HIV infection (odds ratio 4.5; 95% confidence interval 2.5–8.3 and odds ratio 4.5; 95% confidence interval 2.0–10.3, respectively). Mean hemoglobin levels were lower (standardized mean difference; 0.79; 95% confidence interval 0.47–1.10). These differences were observed in both western and tropical settings. Anemia incidence ranged from 0.41 to 0.44 per person-year. There was limited data on more severe anemia (hemoglobin <7 or <5 g/dl). As anemia was frequently identified as an independent risk factor for disease progression and death, we next reviewed the limited data to formulate better strategies. Failure of erythropoiesis was the most important mechanism for anemia in HIV-infected children. Therapeutic options include highly active antiretroviral therapy and prevention or treatment of secondary infections. Erythropoietin can improve anemia in children, but it has not been evaluated in developing countries. Micronutrient supplementation may be helpful in individual children. The potential benefits or risks of iron supplementation in HIV-infected children require evaluation.Anemia is a very common complication of pediatric HIV infection, associated with a poor prognosis. With the increasing global availability of highly active antiretroviral therapy, more data on the safety and efficacy of possible interventions in children are urgently needed.