PURPOSE OF REVIEW: Irritable bowel syndrome (IBS) is a highly prevalent functional gastrointestinal (GI) disorder with negative impact on quality of life and it represents a substantial economic burden on healthcare cost. The medical management of IBS is symptom directed. This review provides an update related to clinical trial data for novel treatment modalities in IBS targeting the gut epithelium secretagogue receptors and channels. RECENT FINDINGS: The new Rome IV criteria define functional gastrointestinal disorders (FGID) as disorders of the gut-brain interaction. Pharmacological treatment modalities for IBS target gastrointestinal receptors and ion channels, peripheral opioid receptor, gut serotonin receptors, and the gut microbiome. New targeted pharmacotherapies have shown efficacy and safety in the treatment of patients with IBS. SUMMARY: Diagnostic criteria for FGID, including IBS, have been revised in Rome IV and are defined as gut-brain disorders. Newly approved pharmacotherapy options with proven efficacy and acceptable side-effect profiles are available for the symptom-based management of IBS.