Kaposi sarcoma-associated herpesvirus (KSHV) can establish latent infection in host cells. The latently infected cells can survive and proliferate with a few viral genes expressed. However, in some Kaposi sarcoma cells, KSHV undergoes a productive life cycle and causes cell lysis. A new study (see the related article beginning on page 124) demonstrates that, after KSHV infection or introduction of viral plasmids into host cells, viral DNA is rapidly lost. Lytic virus production with ensuing infections could balance the loss of the viral plasmids to maintain the virus in cancer cells.