Pediatric HIV/AIDS has become less of a problem in resource-rich countries as the number of perinatal infections has reduced dramatically since the advent of antiretrovirals, resulting in the effective prevention of mother-to-child transmission. In resource-limited settings, however, pediatric HIV infection remains a colossal problem; a separate review in this same issue of Expert Review of Anti-Infective Therapy examines the international aspects of pediatric HIV/AIDS. Treatment of HIV infection in children differs from that in adults in the use of immunologic markers and owing to drug pharmacokinetics and age-related adherence issues. This review, geared for the general pediatrician or family practitioner who may see the HIV-positive child in the clinic or the hospital, summarizes the most recent pediatric data and guidelines for the testing and treatment of HIV, including the US NIH guidelines released in February 2008. Treatment-experienced patients, who should be cared for by pediatric HIV specialists, are not addressed here specifically. Adolescents, infected either perinatally or sexually, with their own unique issues, deserve a separate review.