Human herpesvirus-8/Kaposi’s sarcoma-associated herpesvirus infection is associated with three proliferative disorders in immunocompromised patients – Kaposi’s sarcoma, primary effusion lymphoma and multicentric Castleman’s disease. These disorders often develop in patients with advanced AIDS who present a number of therapeutic challenges, underscoring the importance of continuing efforts dedicated to basic and clinical research in this field. In the era of highly active antiretroviral therapy, the incidence of AIDS and Kaposi’s sarcoma has considerably decreased, presumably due to enhanced anti-Kaposi’s sarcoma-associated herpesvirus immune responses, whereas the situation with primary effusion lymphoma and multicentric Castleman’s disease is more complex. Based on advances in the understanding of Kaposi’s sarcoma-associated herpesvirus-related disorders and availability of antiretroviral agents, current and future therapeutic approaches will be discussed.