Epstein-Barr virus is a potent mitogen for human B lymphocytes and is associated with a large number of human malignancies. This large virus expresses several genes that may contribute to the transformed phenotype of infected cells and it possesses multiple strategies for the inhibition of apoptosis. The interferon-inducible protein kinase PKR is an important target for the anti-apoptotic actions of the virus and its activity is regulated by the small untranslated RNA, EBER-1. This review summarizes the mechanisms of action of EBER-1 and other Epstein-Barr virus gene products in the regulation of apoptosis, and presents a model of how EBER-1 exerts its effects on PKR activity.