Kaposi's sarcoma-associated herpesvirus (KSHV) or human herpesvirus-8 (HHV-8) is a newly identified herpesvirus. KSHV is an important pathogen capable of causing disease that affects all age groups worldwide. KSHV is etiologically associated with all forms of Kaposi's sarcoma (KS), body cavity lymphomas, and multicentric Castleman disease (MCD). The use of highly active antiretroviral therapy (HAART) since 1996 has markedly reduced the prevalence of KS in western countries, but because 99% of the 40 million patients with AIDS in the world cannot afford HAART, KSHV pathogenesis is still a very common problem. In this chapter, we delineate some of the latest findings about KSHV infection and pathogenesis.