Irritable Bowel Syndrome (IBS) is multifactorial in its etiology and heterogeneous in its clinical presentation and pathogenesis. It is recognized that inflammation plays an important role in symptom generation, at least in a subset of patients with IBS. Previous gastroenteritis has been identified as the most important risk factor for IBS, and several studies reported that a substantial proportion of patients with gastrointestinal infection develops IBS symptoms,which can persist for several years. Recent studies have demonstrated that a proportion of IBS patients without any history of enteritis has signs of immune activation in the gut. There is clinical overlap between IBS and inflammatory bowel disease (IBD), with IBS-like symptoms frequently reported in patients before the diagnosis of IBD, and a higher than expected percentage reports of IBS symptoms in patients in remission from established IBD. Thus,these conditions may coexist with a higher than expected frequency, or may exist on a continuum, with IBS and IBD at different ends of the same spectrum. This article examines these relation-ships using immune activation and inflammation as a common pathogenic process to IBD and a subset of IBS patients.