Escherichia coli are leading causes of diarrhea in children from less developed areas of the world and in travelers from industrialized countries visiting these regions. They are increasingly recognized as pathogens in high income countries, where the mode of transmission is frequently via food and waterborne vehicles. Based on their pathogenic phenotypes and the diseases that they cause, diarrheagenic E. coli have been classified into 6 groups: enteropathogenic (EPEC), enterotoxigenic (ETEC), enteroinvasive (EIEC), enteroaggregative (EAEC), diffusely adherent (DAEC), and Shiga toxin producing (STEC) (this last group is also termed enterohemorrhagic (EHEC)). The pathogenic mechanisms by which these groups cause diarrhea are often shared, such as the type 3 secretion system found in EPEC and EHEC, and group-specific, such as the production of Shiga toxins. Although their public health importance is large, the diagnosis of diarrheagenic E. coli in patients and populations is still largely limited to research laboratories. Hence, our knowledge of the spectrum of diseases and syndromes that they cause is quite limited. Also, because we cannot readily identify infected patients, there are many difficulties defining modes of acquisition, prevention and treatment strategies, and estimating the burden of infectious sequelae. These infections pose many challenges, and progress will not occur until we improve our diagnostic capabilities for these agents.