Enterohaemorrhagic Escherichia coli (EHEC) are the pathogenic subgroup of Shiga toxin (Stx)-producing E. coli. EHEC can cause non-bloody and bloody diarrhoea, and the haemolytic uraemic syndrome (HUS). HUS is a major cause of acute renal failure in children. E. coli O57:H7 is the predominant, but far from being the only, serotype that can cause HUS. The cascade leading from gastrointestinal infection to renal impairment is complex, with the microvascular endothelium being the major histopathological target. EHEC also produce non-Stx molecules, such as cytolethal distending toxin, which can contribute to the endothelial or vascular injury. Because there are no specific therapies for EHEC infections, efficient reservoir and human preventive strategies are important areas of ongoing investigations. This review will focus on the microbiology, epidemiology, and pathophysiology of EHEC-associated diseases, and illustrate future challenges and opportunities for their control.