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EBV infection can be characterized in three phases: acute, latent and reactivated. Symptoms of reactivated EBV infection differ from those of the primary infection, being associated mainly with malignancies. A unique feature of EBV infection is its ability to establish latency after infection. Replication of EBV can be effectively inhibited by available antiviral drugs, but latent EBV infection is unaffected by any of these conventional antiviral agents regardless of the mode of action. Despite the availability of effective antiviral drugs, treatment for EBV-associated malignancies remains underdeveloped. This monograph will first provide an overview on the biology and virology of EBV infection, the mechanisms of drug action, current status of nucleoside analogs against EBV replication and other classes of drug with different target sites. The second section will discuss the etiologic factors identified for NPC, environmental, genetic and EBV infection.The last section introduces the cytotoxic T-cell targeting immunotherapy and the development of potential therapeutic gene therapy and moves toward establishing novel approaches for treatment of latent EBV infection.