Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV/HHV8) are human gammaherpesviruses that are etiologic in the development of a variety of hematologic disorders. Infection with these viruses occurs worldwide. EBV is ubiquitous and its prevalence approaches 100% in most adult populations. Both viruses establish persistent latent infection in lymphocytes, which is usually benign. However, in the presence of other environmental, genetic, and iatrogenic cofactors, EBV or KSHV infection is associated with a variety of lymphoproliferative diseases and lymphoma. This chapter summarizes the molecular function of genes expressed during latent and lytic infections that may play a role in oncogenesis. Those aspects of viral gene function that prevent apoptosis, enhance proliferation, and escape from immune attack are emphasized, as these are likely to be important in malignant transformation. Copyright 2003 Elsevier Inc. All rights reserved.