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Irritable bowel syndrome (IBS) remains an incompletely understood, common syndrome with significant unmet medical needs. Significant progress has been made in the development of novel therapies aimed at normalizing bowel habit alterations and abdominal discomfort, even though some of the most effective treatments are currently only available for patients under a restricted access program from the FDA. Preclinical evidence supports the potential usefulness of several compounds in development for the treatment of chronic abdominal pain. Recent new evidence for a possible role of altered microflora and altered host microbial interactions may provide new treatment targets in the future.