Functional gastrointestinal disorders (FGIDs) account for at least 40% of all referrals to gastroenterologists. Of the 33 recognized adult FGIDs, irritable bowel syndrome (IBS) is the most prevalent, with a worldwide prevalence estimated at 12%. IBS is an important health care concern as it greatly affects patients’ quality of life and imposes a significant economic burden to the health care system. Cardinal symptoms of IBS include abdominal pain and altered bowel habits. The absence of abdominal pain makes the diagnosis of IBS untenable. The diagnosis of IBS can be made by performing a careful review of the patient’s symptoms, taking a thoughtful history (e.g., diet, medication, medical, surgical, and psychological history), evaluating the patient for the presence of warning signs (e.g., “red flags” of anemia, hematochezia, unintentional weight loss, or a family history of colorectal cancer or inflammatory bowel disease), performing a guided physical examination, and using the Rome IV criteria. The Rome criteria were developed by a panel of international experts in the field of functional gastrointestinal disorders. Although initially developed to guide researchers, these criteria have undergone several revisions with the intent of making them clinically useful and relevant. This monograph provides a brief overview on the development of the Rome criteria, discusses the utility of the Rome IV criteria, and reviews how the criteria can be applied clinically to diagnose IBS. In addition, a diagnostic strategy for the cost-effective diagnosis of IBS will be reviewed.