Irritable bowel syndrome (IBS) is a complex disorder clinically characterized by abdominal pain and altered bowel habit. Its pathogenetic mechanisms are still incompletely known; genes, psychosocial factors, changes in gastrointestinal motility and visceral hypersensitivity are traditionally thought to play a crucial role in symptom generation. Recent studies have identified new additional factors that can interact with the established mechanisms. Dysregulation of brain-gut axis, gastrointestinal infection, low-grade infiltration and activation of mast cells in the intestinal mucosa with consequent release of bioactive substances, and altered serotonin metabolism are the emerging factors of IBS pathogenesis. Finally, modification of small bowel and colonic microflora and altered gas balance may be of relevance in at least some subgroups of IBS patients. New therapies can be developed only on the basis of a better understanding of the heterogeneous picture of the pathophysiology of IBS.