Irritable bowel syndrome (IBS) is one of the most common diagnoses made by gastroenterologists and primary care providers alike, and yet the underlying mechanism remains poorly understood. Family and twin studies suggest that IBS may have a genetic basis. Several candidate gene association studies have been performed, but thus far, they have failed to clearly identify an “IBS gene.” Epidemiological studies are needed to facilitate phenotype definition and identify relevant environment risk factors that will need to factor in gene and environment interactions in all future genetic studies. As genetic research in IBS is relatively nascent, much opportunity, as well as many challenges, exists in identifying the genes responsible for IBS.