Following Epstein and colleagues' ground-breaking discovery of Epstein-Barr virus by electron microscopy of Burkitt's lymphoma cell lines, there came the observation that Epstein-Barr virus induces immortalization of B cells in vitro. Thus, initial hopes were of a virus confined to equatorial Africa with a causal link to a particular subtype of childhood lymphoma. Over the past 40 years there has been great progress towards understanding the biology and epidemiology of Epstein-Barr virus, which conclusively show that these early ideas were overly simplistic. It is now known that Epstein-Barr virus has a seroprevalence of approximately 95% worldwide, and persists for life within host B lymphocytes. Infection in New World primates leads to lymphoma and inoculation of peripheral blood mononuclear cells from Epstein-Barr virus-seropositive subjects into severe combined immunodeficiency mice results in B-cell lymphoproliferative disorders. Epstein-Barr virus is now known to be implicated in a range of lymphoid and other malignancies, and this association will be the subject of this review.