There are a number of reasons to establish the accurate diagnosis of irritable bowel syndrome (IBS): to relieve patient uncertainty; to avoid adverse effects of unnecessary medications or treatments; to avoid unnecessary diagnostic procedures and surgeries; to conserve limited healthcare resources; and, of course, to initiate the most appropriate treatment. However, making the diagnosis of IBS remains difficult because it is clinically heterogeneous, no biological marker to detect it exists, many other diseases share the same clinical manifestations and it is often difficult for both physicians and patients to accept the uncertainty of a symptom-based diagnosis. Different diagnostic criteria have been developed during the last 4 decades but none have proved to be an ideal method of accurately diagnosing IBS. Just as importantly, physicians are frequently unaware of published guidelines or consciously ignore these diagnostic criteria. Most clinicians still believe IBS is a diagnosis of exclusion and not a positive diagnosis based on history, physical examination, use of published diagnostic criteria such as the Rome III criteria, and the absence of alarm features. In the sections to follow we will address the inherent difficulties of diagnosing IBS, highlight the importance of symptom-based diagnoses to help reign in soaring healthcare costs, and discuss future strategies that may enable a more cost-efficient diagnosis of IBS.