Kaposi's sarcoma (KS) has long been suspected of having an infectious etiology on the basis of its unusual epidemiology, histopathology, and natural history. Nearly a decade ago, a novel herpesviral genome was discovered in KS biopsies, and since that time strong epidemiologic evidence has accumulated correlating infection with this KS-associated herpesvirus (KSHV, also known as human herpesvirus 8) with the development of the disease. Here we review the evidence linking KSHV infection to KS risk and discuss current notions of how KSHV gene expression promotes the development of this remarkable neoplasm. These studies show that both latent and lytic viral replicative cycles contribute significantly-but differently-to KS development. The studies also highlight mechanistic differences between oncogenesis caused by KSHV and that caused by its distant relative Epstein-Barr virus.