Irritable bowel syndrome is a functional gastrointestinal disorder affecting up to 3-15% of the general population in western countries. It is characterised by unexplained abdominal pain, discomfort, and bloating in association with altered bowel habits. The pathophysiology of irritable bowel syndrome is multifactorial involving disturbances of the brain-gut axis. The pathophysiology provides the rationale for pharmacotherapy: abnormal gastrointestinal motor functions, visceral hypersensitivity, psychosocial factors, autonomic dysfunction, and mucosal immune activation. Understanding the mechanisms, and their mediators or modulators including neurotransmitters and receptors have led to several therapeutic approaches including agents acting on the serotonin receptor or serotonin transporter system, antidepressants, novel selective anticholinergics, alpha-adrenergic agonists, opioid agents, cholecystokinin-antagonists, neurokinin-antagonists, somatostatin receptor agonists, corticotropin releasing factor antagonists, chloride channel activators, guanylate cyclase-c agonists, melatonin, atypical benzodiazepines, antibiotics, immune modulators and probiotics. The mechanisms and current evidence regarding efficacy of these agents are reviewed.