Epstein-Barr virus (EBV), first isolated from a cultured Burkitt’s lymphoma cell line in 1964, is now recognized as a ubiquitous human herpesvirus. EBV infection during the early infantile period is generally subclinical. However, one-half to two-thirds of primary EBV infection in adolescents and adults manifest infectious mononucleosis. Defenses against EBV infection include secretory components such as mucus and secretory immunoglobulin A, epithelial barriers, interferons, natural killer cells, human histocompatibility leukocyte antigen-restricted or non-restricted cytotoxic T cells, neutralizing antibodies, and antibody-dependent cell-mediated cytotoxicity. Clinical usefulness of Production of Interferon (IFNs) for treating a variety of diseases has been shown by numerous investigators. The immunopathogenetic mechanisms responsible for certain diseases and the value of treating the patients with IFNs remain unclear. The discovery of IFNs commenced with noting a response of cells to viral infection. The precise pathogenetic mechanism(s) responsible for various diseases should be clarified and the possible impact of IFNs should be considered prior to their therapeutic use.