Pediatric human immunodeficiency virus (HIV) infection is now the seventh leading cause of death in U.S. children 1 to 14 years of age and the leading cause of death in children 2 to 5 years of age in many U.S. cities. The key to enhancing the quality and duration of life in HIV-infected children is to recognize and diagnose HIV infection as early as possible and to initiate prophylactic and antiretroviral therapies. Most of the medical treatment of these children can be conducted in a primary care setting if (a) primary care practitioners are informed of current treatment regimens and (b) adequate pediatric HIV consultation service is available. This article reviews the primary care of HIV-infected children including early diagnosis, current treatment options, and the complex psychosocial issues associated with caring for these children.