Patients with irritable bowel syndrome (IBS) account for >$20 billion in direct and indirect costs annually, a large portion of which relates to making the diagnosis. The diagnosis of IBS is challenging because symptoms can vary between patients and overlap with those of other disorders. This review examines the current diagnostic approach in IBS and discusses new tools that may improve diagnostic confidence earlier in the process. The prevalence of organic disease among patients who meet symptom-based criteria for IBS (eg, Rome III) is generally low; therefore, in the absence of "alarm features," the probability for organic disease is very low. Increased public awareness of IBS symptoms and physician awareness of symptom-based criteria for IBS are needed to facilitate earlier diagnosis. Accumulating evidence suggests that fecal and/or serum biomarkers may be helpful in differentiating IBS from non-IBS disorders. These tools may help minimize unnecessary testing and diagnostic delays. As biomarkers are further studied and developed, they are likely to become an integral part of the diagnosis of IBS and reduce the potential for incorrect diagnosis and treatment delays.