Herpesviruses are large double-stranded DNA viruses that are characterized by lifelong latency. Epstein-Barr virus (EBV), the recently discovered Kaposi's sarcoma associated herpesvirus (KSHV), also referred to as human herpesvirus-8 (HHV-8), and the simian Herpesvirus saimiri (HVS) are associated with malignant lymphoproliferative diseases. These viruses establish latent infection in lymphoid cells. During latency only a few viral genes are expressed and the viral genome persists as a multicopy circular episome. The episome contains repetitive sequences that serve as multiple cooperative binding sites for the viral DNA binding proteins Epstein-Barr virus nuclear antigen 1 (EBNA-1) of EBV and latency-associated nuclear antigen (LANA1) of KSHV and HVS, which are expressed during latency. The oligomerized proteins associate with the viral genome and tether it to host chromosomes, assuring continual lifelong persistence of the virus.