Enteroaggregative Escherichia coli (EAEC) are among the most prevalent enteric pathogens worldwide. The pathotype has been implicated in endemic diarrhea in both developing and industrialized populations, epidemic diarrhea, and traveler’s diarrhea. A recent outbreak of Shiga toxin-producing EAEC adds a new dimension to the epidemiology of this pathotype. Although the pathogenesis of this pathotype is not fully understood, a number of putative virulence factors have been described. The aggregative adherence fimbriae (AAF) are mucosal adhesins that also elicit inflammatory responses from infected mucosal surfaces. Expression of AAF adhesins is induced by the transcriptional activator AggR, which activates expression of several other secreted, but as yet relatively cryptic, proteins. EAEC-induced histopathology includes exfoliation of enterocytes, which has been linked to the action of serine protease autotransporter toxins. Epidemiologic evidence supports a model of EAEC pathogenesis comprising the concerted action of multiple virulence factors.