Epstein-Barr virus (EBV) is a member of the human herpesvirus family and, like many other herpesviruses, maintains a lifelong latent association with B lymphocytes and a permissive association with stratified epithelium in the oropharynx. Clinical manifestations of primary EBV infection range from acute infectious mononucleosis to an asymptomatic persistent infection. EBV is also associated with a number of malignancies in humans. This review discusses features of the biology of the virus, both in cell culture systems and in the natural host, before turning to the role of the immune system in controlling EBV infection in healthy individuals and in individuals with EBV-associated diseases. Cytotoxic T cells that recognize virally determined epitopes on infected cells make up the major effector arm and control the persistent infection. In contrast, the options for immune control of EBV-associated malignancies are more restricted. Not only is antigen expression restricted to a single nuclear antigen, EBNA1, but also these tumor cells are unable to process EBV latent antigens, presumably because of a transcriptional defect in antigen-processing genes (such as TAP1 and TAP2). The likelihood of producing a vaccine capable of controlling the acute viral infection and EBV-associated malignancies is also discussed.