Epstein-Barr virus (EBV) infects and persists for life in the majority of the human population. Persistence is achieved through a combination of strictly regulated programs of latent infection in B-cells and chronic reactivation of virus replication in lymphoid tissue and mucosal surfaces. The resulting multiple patterns of virus-host interaction have selected unique strategies of immune escape. T-cell mediated immunity plays a central role in the control of EBV latency and several immune escape mechanism that protect the virus at this stage of its life circle have been characterized in details. In contrast, the contribution of innate immunity and the immune regulation of productive infection are largely unexplored areas that may yield important clues on the establishment and maintenance of EBV persistence. This review summarizes well known and emerging mechanisms of EBV immune escape that may reveal new strategies of immunoregulation and promote new approaches to the prophylaxis and treatment of EBV associated diseases.