Kaposi sarcoma-associated herpesvirus [KSHV, also known as human herpesvirus 8 (HHV-8)] is the most recently identified member of the human herpesvirus family. Kaposi sarcoma (KS), primary effusion lymphoma, and multicentric Castleman disease are all associated with KSHV infection. Although the incidence of KS has declined dramatically in areas with access to highly active antiretroviral therapy, it remains the most common AIDS-associated malignancy in the developed world and is one of the most common cancers in developing nations. Current treatment options for KSHV-associated disease are ineffective, unavailable, or toxic to many affected persons. A growing body of basic science, preclinical, and observational data suggests that antiviral medications may play an important role in the prevention and treatment of KSHV-associated disease.