HIV infection in the United States appeared early in the 1980s, when previously healthy homosexual men manifested opportunistic infections attributable to apparent underlying immunodeficiency. After these initial isolated reports, there appeared many other groups of patients at risk for development of this devastating disease. From these meager beginnings, the problem has escalated exponentially. HIV infection can affect every system in the human body. Since the era of highly active antiretroviral therapy, however, the prevalence of opportunistic infections and HIV-AIDS clinical manifestations has declined dramatically. In addition to antiretroviral therapy, management of HIV-infected persons requires knowledge of the extent of system involvement, as well as highly active antiretroviral therapy-related adverse effects, so as to recognize complications and initiate appropriate intervention. In the following review we will attempt to comprehensively summarize the clinical manifestations of HIV infection for both pediatric and adult populations.