Human herpesvirus 8 (HHV-8) was detected in 1994 in biopsies of Kaposi's sarcoma (KS) tissues from a patient with AIDS. The evidence that HHV-8 infection is etiologically related to the development of KS is compelling. Essentially all patients with KS of any epidemiological type have serological evidence of HHV-8 infection. About 30%-40% of homosexual men infected with human immunodeficiency virus (HIV) are seropositive for HHV-8; rates are lower (<10%) among HIV-infected women, hemophiliacs, and injection drug users. Among homosexual men, the probability of HHV-8-seropositivity is directly proportional to the numbers of previous male sex partners, which suggets that HHV-8 is a sexually transmitted infection. Although HHV-8 is detectable in saliva and semen, the exact mechanism of transmission is not known. A reduction in KS incidence among patients with AIDS in the 1980s has been attributed to lower rates of HHV-8 transmission that resulted from alterations in sexual behaviors. A further decline in KS incidence has been associated with the use of antiretroviral therapy. Antiretroviral therapy to control HIV replication and to limit the associated immunodeficiency is currently the best approach for preventing KS in persons infected with HHV-8 and HIV.