Epstein-Barr virus (EBV) is associated with several different types of aggressive non-Hodgkin lymphoma (NHL). Individuals with primary or secondary immunodeficiency are susceptible to developing B cell lymphoproliferation due to outgrowth of EBV-infected B cells that express type III latency characterized by expression of all nine latent-cycle EBV antigens. These cells would normally be susceptible to control by EBV-specific T cells, and strategies to restore EBV-specific immune responses may be effective therapeutically. EBV-associated lymphomas occurring in individuals who do not have a known immunodeficiency include NK and T malignancies with cytotoxic phenotypes, sporadic cases of B-NHL and lymphomatoid granulomatosis. These malignancies respond poorly to standard chemoradiotherapy, and immunotherapeutic or pharmacologic strategies targeting EBV are being explored.