Viruses have evolved many distinct strategies to avoid the host’s apoptotic response(1,2). Here we describe a new family of viral inhibitors (v-FLIPs) which interfere with apoptosis signalled through death receptors(3) and which are present in several gamma-herpesviruses (including Kaposi’s-sarcoma-associated human herpesvirus-8), as well as in the tumorigenic human molluscipoxvirus(4). v-FLIPs contain two death-effector domains which interact with the adaptor protein FADD(5,6) and this inhibits the recruitment and activation of the protease FLICE(7,8) by the CD95 death receptor(3). Cells expressing v-FLIPs are protected against apoptosis induced by CD95 or by the related death receptors TRAMP(9-12) and TRAIL-R. The herpesvirus saimiri FLIP is detected late during the lytic viral replication cycle, at a time when host cells are partially protected from CD95-ligand-mediated apoptosis, protection of virus-infected cells against death-receptor-induced apoptosis may lead to higher virus production and contribute to the persistence and oncogenicity(13) of several FLIP-encoding viruses.