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Kaposi's sarcoma-associated herpesvirus (KSHV) is the 8th human herpesvirus discovered in 1994. After primary infection, KSHV establishes latency and, in the context of immunosuppression, has been associated with specific malignancies: Kaposi's sarcoma (KS), primary effusion lymphoma (PEL) and multicentric Castleman's disease (MCD). Seroepidemiological surveys suggest that KSHV is not a ubiquitous virus and several transmission routes and risk factors must exist to explain its global distribution. The increased risk of KSHV-associated cancers in human immunodeficiency virus (HIV)-infected individuals, and the decrease of KS incidence after the introduction of highly active anti-retroviral therapy (HAART) in 1997 suggest that cellular immunity plays an important role in controlling KSHV. In this thesis, seroepidemiological studies were conducted in African, Middle Eastern, Mediterranean European and South American countries to determine the infection rate, and to determine risk factors and possible routes of KSHV transmission. A new quantitative real-time PCR method was developed to detect KSHV in clinical samples. This assay has diagnostic and prognostic implications for the management of KSHV-associated diseases. Anti-viral and immunological responses were measured and analysed, and cellular immune responses to KSHV were demonstrated in a cohort of HIV infected individuals undergoing HAART treatment. The interaction between KSHV and HIV was evaluated and the impact of HAART on KSHV immune reconstitution was investigated.