Enterotoxigenic Escherichia coli (ETEC) are a major cause of diarrheal illness in developing countries, and perennially the most common cause of traveller's diarrhea. ETEC constitute a diverse pathotype that elaborate heat-labile and/or heat stable enterotoxins. Recent molecular pathogenesis studies reveal sophisticated pathogen-host interactions that might be exploited in efforts to prevent these important infections. While vaccine development for these important pathogens remains a formidable challenge, extensive efforts that attempt to exploit new genomic and proteomic technology platforms in discovery of novel targets are presently ongoing.