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Long neglected and considered a difficult ecosystem to study, several developments have recently converged to renew interest in studying the normal gut microbiota. These include molecular methods of studying the microbiota, improved understanding of host–microbe interactions in health and disease, and the potential for therapeutic manipulation of the microbiota. This review focuses on the most recent work in these areas.Host–microbe signaling in the gut is critical for normal development and homeostasis of the gastrointestinal mucosa. The molecular basis of these interactions promises new therapeutic strategies for various disorders. Particularly noteworthy has been the emergence of evidence for the role of enteric bacterial metabolism in the pathogenesis of disorders ranging from functional and inflammatory bowel diseases to human obesity. Metagenomic and metabolomic profiling of the microbiota, although at an early stage, has demonstrated the range and complexity of the gut ecosystem and cast insights into several diseases. The molecular basis of host–microbe dialogue and the mechanisms by which the host contains enteric bacteria within the lumen has immediate relevance to infectious and chronic inflammatory bowel disease.Improved understanding of the normal gut microbiota has made the therapeutic manipulation of the gut ecosystem a valid and realistic future prospect.