Epstein-Barr virus (EBV) infection is a common feature of B cell lymphoproliferative disorders (LPDs), including diffuse large B cell lymphoma. Approximately 10 % of DLBCLs are EBV-positive, with the highest incidence in immunocompromised and elderly patients. Here, we review the clinical, genetic, and pathologic characteristics of DLBCL and discuss the molecular role of EBV in lymphoma tumorigenesis. Using EBV-positive DLBCL of the elderly as a model, we describe the key features of EBV-positive DLBCL. Studies of EBV-positive DLBCL of the elderly demonstrate that EBV-positive DLBCL has a distinct biology, related to both viral and host factors. The pathogenic mechanisms noted in EBV-positive DLBCL of the elderly, including enhanced NFκB activity, are likely to be a generalizable feature of EBV-positive DLBCL. Therefore, we review how this information might be used to target the EBV or its host response for the development of novel treatment strategies.