The description of the de novo development of irritable bowel syndrome following an episode of bacterial gastroenteritis (pos-infectious irritable bowel syndrome) illustrated the potential for a luminal factor (a bacterial pathogen) to cause this common gastrointestinal ailment. As a consequence of these and other observations, as well as results of experiments involving animal models, the enteric flora and the immune response that it generates in the host have, somewhat surprisingly, come centre-stage in irritable bowel syndrome research, given their potential to induce the pathophysiological changes that are associated with irritable bowel syndrome. While evidence for immune dysfunction both in the mucosa and systemically continues to accumulate, methodological limitations have hampered a full delineation of the nature of the microbiota in irritable bowel syndrome. The latter is eagerly awaited and may yet provide a firm rationale for the use of certain probiotics and antibiotics in irritable bowel syndrome, whose benefits have now been described with some consistency. Despite its prevalence, there is a striking lack of effective therapeutic options for irritable bowel syndrome. While there is reason for optimism in the management of irritable bowel syndrome with several promising new agents currently undergoing clinical trials, confirmation of the efficacy and safety of these agents in wider patient populations is awaited. A clearer understanding of the physiopathologic mechanisms underlying irritable bowel syndrome, as well as of interrelationships between irritable bowel syndrome and other gastrointestinal and non-gastrointestinal disorders, will likely be required before effective drug therapies can be found.