The discovery of Kaposi's Sarcoma-associated herpesvirus/human herpesvirus-8 (KSHV/ HHV-8) and subsequent studies of this virus have provided a body of evidence that support the concept that this is an etiologic agent for Kaposi's sarcoma (KS). Several studies have indicated that this virus may also be a causal agent for primary effusion lymphoma (PEL) and Castleman's disease as well. First generation serologic assays for HHV-8 have now been developed. The preponderance of data suggest that the incidence of HHV-8 infection is highest in populations at risk for KS: male homosexuals, immunosuppressed patients, and those who live in endemic regions. HHV-8 encodes for functional homologs of human proteins that may play a role in the development of disease. As we learn more about the steps by which this virus can lead to KS and/or other diseases, rational therapies and preventative strategies may be possible.