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Human herpes virus 8 (HHV-8) is a geographically limited virus that causes neoplastic and nonneoplastic diseases predominantly in endemic regions. Primary HHV-8 infection, which is usually asymptomatic in immunocompetent individuals, result in lifelong latency. When the equilibrium between virus and host immunity is disturbed, such as after organ transplantation, HHV-8 may activate molecular pathways that drive oncogenesis. Kaposi's sarcoma, primary effusion lymphoma, and Castleman's disease are the major malignancies associated with HHV-8. The incidences of these neoplastic pathologies mirror the geographic HHV-8 seroprevalence, and certain groups of patients are at higher risk. In this context, the risk of HHV-8 and its clinical disease is highest in immunocompromised patients, including transplant recipients. Solid organ transplant recipients from HHV-8 endemic regions may develop HHV-8 reactivation or primary infection and manifest with Kaposi's sarcoma or less commonly primary effusion lymphoma and Castleman's disease; these neoplastic diseases are reported much less commonly in low-prevalent areas. There is currently no standard method of screening for HHV-8 infection in the transplant setting, although HHV-8 polymerase chain reaction is available to confirm clinical suspicion of infection. Management of HHV-8-associated diseases entails primarily a reduction in the degree of pharmacologic immunosuppression and, in some cases, chemotherapy may be required. The mammalian target of rapamycin inhibitor sirolimus may have the potential for management because of its antiproliferative properties. The role of antiviral drugs for HHV-8 prevention and treatment is yet to be defined.