Irritable bowel syndrome (IBS), the most common functional gastrointestinal disorder referred to gastroenterologists, affects 7-10% of the general population worldwide. The lack of suitable disease-defining biological markers coupled with a poorly understood underlying pathophysiology complicates patient diagnosis and seriously hampers drug discovery efforts. Over the past few years, a number of potential biomarkers have emerged, and in this review we critically evaluate such candidates. In particular, we highlight the increasing number of studies supporting a low-grade immune activation in IBS and consider how the latest preclinical developments can contribute to the development of more robust and reliable biological markers of this disorder. The successful identification of biomarkers is critical to progressing our understanding of IBS and addressing the unmet therapeutic needs of this debilitating condition.