Irritable bowel syndrome (IBS) may result from a dysfunctional interaction between the indigenous flora and the intestinal mucosa, which in turn leads to immune activation in the colonic mucosa. Some propose that bacterial overgrowth is a common causative factor in the pathogenesis of symptoms in IBS; others point to evidence suggesting that the cause stems from more subtle qualitative changes in the colonic flora. Bacterial overgrowth will probably prove not to be a major factor in what will eventually be defined as IBS. Nevertheless, short-term therapy with either antibiotics or probiotics seems to reduce symptoms among IBS patients. However, in the long term, safety issues will favor the probiotic approach; results of long-term studies with these agents are eagerly awaited.