The discovery of human herpesvirus 8 (HHV-8) has opened a new field in the biology and in the clinical definition of HHV-8-associated diseases. Various aspects of epidemiology, laboratory diagnosis and treatment of HHV-8 infection are still controversial. This review will summarise the most recent findings on the modalities of viral transmission in geographic areas where the virus is endemic as compared with those where the infection is sporadic. The studies on the interactions between HHV-8 and Epstein-Barr virus in the promotion of tumorigenesis will be then emphasised. This review will finally address the problems still open in the laboratory diagnosis and in the definition of antiviral drug susceptibility of HHV-8. Solving satisfactorily these issues will be necessary to better understand the epidemiology of HHV-8 infection, to reduce the risk of viral transmission, the progression of infected hosts to HHV-8-related malignancies and to achieve more active treatment options for these clinical conditions.