Irritable bowel syndrome is one of several highly prevalent functional gastrointestinal disorders (FGID) displaying symptoms of gastrointestinal dysmotility and visceral hypersensitivity. Substantial overlap of symptoms and comorbidities occur not only between irritable bowel syndrome and other FGID but also with gastrointestinal disorders that are not related to motility (eg, celiac disease and lactose intolerance) and to somatic conditions (eg, fibromyalgia and chronic fatigue syndrome). Pathogenic mechanisms common among FGIDs may include alternations in intestinal and colonic microflora. Evidence is also emerging of an interplay between gut immune cells/activity and alternations in motility, secretion, and sensation. The role of cytokine activity and inflammation is important in this regard. As recommended by Rome III, diagnostic testing should be guided by the patient's age, primary symptom characteristics, and other clinical and laboratory features. The high prevalence of coexisting conditions suggests the need to routinely assess patients for related disorders. Treatment should be based on an individualized evaluation, explanation, and reassurance.