Purpose of review Irritable bowel syndrome (IBS) is a highly prevalent gastrointestinal disorder with negative impact on quality of life and it represents a substantial economic burden on healthcare cost. The medical management of IBS remains largely symptomatic. This review provides an update related to the most recently published diagnostic Rome IV criteria for IBS and clinical trial data for novel treatment modalities in IBS targeting the peripheral opioid receptors of the enteric nervous system and the gut microbiota. Recent findings The new Rome IV criteria define functional gastrointestinal disorders as disorders of the gut-brain interaction. In addition to previously introduced pharmacological treatment modalities for IBS with constipation (IBS-C) with synthetic peptides and small molecules targeting gastrointestinal receptors and ion channels, the newly Food and Drug Administration-approved mixed peripheral opioid receptor agonist/antagonist eluxadoline and the nonabsorbable antibiotic rifaximin demonstrate efficacy and safety in the treatment of IBS with predominant diarrhea (IBS-D). Summary Diagnostic criteria for functional gastrointestinal disorders, including IBS, have been revised in Rome IV and are defined as gut-brain disorders. The mixed peripheral opioid receptor agonist/antagonist eluxadoline and the antibiotic rifaximin have been recently Food and Drug Administration approved for the treatment of diarrhea-predominant IBS (IBS-D) with proven efficacy and acceptable side-effect profiles.