The clear delineation of a post-infective variety of IBS, as well as the description, in a number of studies, of evidence of low-grade inflammation and immune activation in IBS, suggest a role for a dysfunctional relationship between the indigenous flora and the host in IBS and, accordingly, provide a clear rationale for the use of probiotics in this disorder. Other modes of action, including bacterial displacement and alterations in luminal contents, are also plausible. While clinical evidence of efficacy is now beginning to emerge, a review of available trials emphasizes the importance of a clear definition of strain selection, dose and viability. The possible roles of co-therapy or sequential therapy with antibiotics, probiotics, prokinetics, or other agents also deserves further study. The role of the enteric flora is evidently an area of great potential in IBS; we are on the threshold of a new era of research and therapy for this common disorder.