Irritable bowel syndrome (IBS) is a disease of unclear, complex pathophysiology characterised by abdominal pain and discomfort and altered bowel activity. It affects an estimated 10-15% of individuals worldwide and has a large impact on quality of life (QOL) and both direct and indirect healthcare costs. Symptoms of IBS are usually triggered by disruption of gastrointestinal (GI) function secondary to infection, dietary factors, lifestyle changes or psychological stress. While most currently available pharmacological treatments of IBS focus on symptomatic treatment of the syndrome, agents that attempt to address the pathophysiology of the disease, in particular the role of serotonin, have received much attention in recent years. However, there is growing concern that serotonergic agents as a class may be associated with rare, but serious, episodes of ischaemic colitis, with several cases of this complication having been reported in association with use of serotonergic agents that have reached the market. Thus, there remains an important need for safe and effective agents that treat the symptoms of IBS. Otilonium bromide, a spasmolytic agent, has been widely used worldwide and has been found to be effective and safe for managing abdominal pain. Clinical trials indicate that it improves baseline abdominal pain and distension, and is particularly effective in reducing diarrhoea. Combining otilonium bromide with benzodiazepines, such as diazepam, may improve the efficacy of the agent with respect to GI symptoms, while also treating underlying anxiety disorders. More research is required to confirm the efficacy and mechanisms of action associated with this combination therapy in IBS. Safety data from clinical trials and postmarketing sources indicate that otilonium bromide is well tolerated, with a safety profile comparable to placebo in clinical trials and only two reported cases of adverse reactions (urticaria) among 10-year postmarketing data. This article reviews the pathophysiology and treatment of IBS with a particular focus on the role of otilonium bromide in the management of this condition.