The emergence of enterohaemorrhagic Escherichia coli (EHEC) as major human pathogens began with the identification of serotype O157:H7 in the early 1980s as the cause of various food-borne outbreaks of severe intestinal disease. The key virulence factors include verocytotoxins (Vt) and effectors and adhesins associated with type III secretion systems. Tracing the origins of human outbreaks reveals that the primary source of this organism is the ruminant gastro-intestinal tract and a variety of transmission routes to humans have been identified. The epidemiology of E. coli O157:H7 within cattle and other ruminants has been studied extensively and the prevalence of non-O157:H7 serotypes contrasts with the observed dominance of E. coli O157:H7 amongst human EHEC isolates. Although there is some evidence that EHEC cause disease in young animals, the high prevalence of Vt within healthy ruminants suggests that this is not a virulence factor within these species. An understanding of the mechanisms underpinning EHEC persistence within their natural reservoir hosts and the development of a molecular understanding of EHEC biology and evolution could eventually allow a reduction in the incidence of human disease and may reduce future threats. The use of animal models to replicate and study human EHEC pathogenesis is described.