Enterohaemorrhagic Escherichia coli (EHEC) cause diarrhoea, haemorrhagic colitis and the haemolytic uraemic syndrome (HUS). EHEC cause sporadic, epidemic, and occasionally fatal infections in Germany and worldwide. The most probable natural reservoirs of EHEC are domestic cattle (in which these organisms cause no disease), but wild animals also excrete EHEC asymptomatically. Humans (chiefly children) acquire EHEC from contact with animals (e. g. in petting zoos) or indirectly, by consuming food or water contaminated with these pathogens. Acid resistant EHEC survive the acidic human stomach, colonize the intestines, and produce Shiga toxins. Current models suggest that Shiga toxins preferentially bind to microvascular endothelial cells of the renal glomeruli and the brain and inhibit protein synthesis, or possibly injure eukaryotic cells via other mechanisms. Resulting microangiopathy, therefore, forms the pathological basis of HUS. Additionally, non-Shiga toxin effectors produced by EHEC, including the LEE-encoded proteins, EHEC-haemolysin, cytolethal distending toxin (CDT), the serine protease EspP, subtilase cytotoxin, and iron-acquisition molecules are also postulated to play roles in virulence. Our evolving understanding of EHEC pathogenesis now compels us to test the hypothesis that HUS is a multifactorial consequence of EHEC infection, that involves not only Shiga toxins, but a repertoire of EHEC virulence factors that synergistically cause profound vascular and organ injury.