Irritable bowel syndrome (IBS) is a common gastrointestinal disorder characterized by abdominal pain and altered bowel function. Few agents are available for the treatment of IBS. Historically, one impediment to the development of agents to treat IBS was lack of a uniform and robust clinical trial design. Studies occurred with different durations of treatment, endpoints and with different target populations. Great advances have been made over the past decade in trial design including: optimal duration of study, mode of data collection, populations to evaluate and identification of endpoints. Using these refinements, it was possible to demonstrate the efficacy of some new agents. These advances are illustrated by a review of trials with kappa opioid agonists and atypical benzodiazepine antagonists, which appear to be promising new classes of treatments for symptoms in IBS.