Introduction: Irritable bowel syndrome with diarrhea (IBS-D) is among the most common functional gastrointestinal (GI) disorders and is associated with impaired quality of life, increased health-care utilization, and significant costs to patients and society. The treatment of IBS is typically hierarchal with initial therapies consisting of dietary and lifestyle modifications. Pharmacotherapy with over-the-counter and prescription medications is also commonly used for symptomatic control in the course of therapy.Areas covered: Three medications are approved by the United States Food and Drug Administration (FDA) for IBS-D, with all of them demonstrating efficacy in randomized, placebo-controlled trials. In this review, the authors discuss the clinical trial data applicable to the current FDA approved IBS-D therapies as well as review data related to new and emerging therapies for this condition.Expert opinion: Clinicians should be familiar with emerging therapies for IBS-D as they may provide benefit to some IBS-D patients. The exact mechanisms of action of many of the emerging agents for IBS-D remain unknown. Despite substantial differences and limitations in the design and quality of supporting studies, there is an increasing body of evidence suggesting that emerging agents may promote meaningful symptom improvement in patients with IBS-D.