The Epstein-Barr virus (EBV) is uniquely associated with a broad range of human malignancies. In spite of their diverse cellular origin, most of these malignancies share common features, including the expression of either some or all of the EBV latent proteins, which can be potentially exploited for immune-based therapies. Here we discuss new and emerging strategies to manipulate the immune response to specifically boost T-cell immunity towards viral proteins that are expressed in EBV-associated malignancies. These strategies are used either alone or as an adjuvant therapy in combination with chemotherapy and/or monoclonal antibodies. Overall, this strategy may serve as a new paradigm for the successful multi-modality treatment of malignancies.