The most common reason for seeing a gastroenterologist is irritable bowel syndrome (IBS). IBS was thought to be a functional disease; however, there are now numerous alternative pathophysiologic pathways that can explain the symptoms. The pathophysiology of IBS is diverse and not well understood. Most current first-line treatments for IBS target the primary symptom and mainly impact one symptom in the symptom complex. The purpose of this study was to summarize the data on new medicines used to treat IBS. We conducted a bibliographic search in Google Scholar and PubMed focused on medication clinical trials in IBS with diarrhea. New medications for IBS with diarrhea target important pathways in the pathophysiology of these disorders, improving both the abnormal bowel habit and other significant symptoms such as abdominal pain and bloating.