Human immunodeficiency viruses types 1 and 2 (HIV-1 and HIV-2) are retroviruses that attack and destroy cells essential to the regulation of immune function, primarily the CD4-bearing lymphocytes. Of the two viruses, HIV-1 accounts for the vast majority of infection, morbidity and mortality in the world. Some newly infected individuals experience a mononucleosis-like syndrome, and all undergo a deterioration of cell-mediated immunity. Although the rate of loss is highly variable, in the absence of treatment the loss is eventually profound enough to produce a fatal acquired immunodeficiency syndrome (AIDS) consisting of a spectrum of opportunistic infections and neoplasms. Since the emergence of AIDS in 1981, HIV-1 has spread by sexual, parenteral, and perinatal routes to reach pandemic proportions. Some 35 million people worldwide are currently infected with HIV-1, but the affected populations vary greatly by geographic, socioeconomic and behavioral factors. Men who have sex with men were initially and still are at high risk, but the infection has had huge numerical impact on heterosexuals in sub-Saharan Africa and Asia and on injection drug users in Eastern Europe, Southeast Asia and urban areas elsewhere. Numerous alternative therapeutic antiretroviral agents combined in increasingly simpler and less toxic regimens have proved capable of suppressing viremia to undetectable levels and often essentially halting the disease process. However, HIV-1 mutates easily and establishes seemingly permanent reservoirs from which the virus has proved difficult to dislodge entirely with even the most aggressive therapy. Nevertheless, international organizations have accepted the challenge of mobilizing to deliver those agents in concerted intervention programs tailored to local epidemiologic and socioeconomic conditions. Primary prevention HIV-1 infection at the population level has depended heavily on implementation of programs for screening of blood supplies, behavioral risk reduction, male circumcision, and administration of vaginal microbicides or systemic suppression of ulcerative genital co-infections. Success has been mixed and slow in coming. Vaccine development has been frustratingly slower. Discovery of a correlate of broadly protective immunity has eluded the most intense vaccinologic research, and trials of early prototype vaccines have been largely disappointing. A more promising preventive strategy has been a byproduct of widespread therapeutic intervention: treat infected individuals to prevent transmission to their uninfected partners, i.e., treatment as prevention. Whether expansive application of this strategy will prove to be the turning point in the battle against HIV/AIDS remains to be seen.