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.