With the emergence of the AIDS epidemic over the last 2 decades and the more recent identification of Kaposi sarcoma-associated herpesvirus (KSHV, Human herpesvirus 8), the genera of rhadinoviruses have gained importance as a family of viruses with oncogenic potential. First recognized in New World primates more than 30 y ago, the rhadinoviruses Saimiriine herpesvirus 2 and Ateline herpesvirus 2 have well-described transforming capabilities. Recently several new species-specific rhadinoviruses of Old World primates have been described, including retroperitoneal fibromatosis herpesvirus and rhesus rhadinovirus (Cercopithecine herpesvirus 17). Molecular analysis of these viruses has elucidated several functionally conserved genes and properties shared with KSHV involved in cellular proliferation, transformation, and immune evasion that facilitate the oncogenic potential of these viruses. This review examines the comparative pathobiology of KSHV, discusses the role of macaque rhadinoviruses as models of human disease, and outlines the derivation of specific pathogen-free animals.