Clinicians are frequently challenged to interpret gastrointestinal symptoms in patients with inflammatory disease (IBD). Irritable bowel syndrome (IBS)-like symptoms are common in patients with IBD and the underlying mechanism is likely to be active or occult inflammation of the bowel rather than co-existing IBS. Biopsychosocial construct and mucosal inflammation, stress, alteration of the hypothalamic-pituitary-adrenal axis, and autonomic dysregulation are contributing factors to IBD-IBS. In particular, low-grade inflammation and immune activation are recent topics regarding the underlying mechanism. Some authors have claimed that inflammation could be a common pathophysiologic factor, in which IBS and IBD might represent the two ends of a wide spectrum of chronic inflammatory conditions. Mast cells, enteroendocrine cells, T cells, and B cells are main effector cells in immune responses. Differentiating IBS symptoms from exacerbation of IBD is important, thus preventing the use of excessive IBD medications, with the potential side effects, or narcotics. Medical treatments with anti-diarrheals, anti-spasmodics, anti-depressants, and anxiolytics can be helpful. However, abuse can lead to medication-dependency and bring about side effects. A healthy, balanced lifestyle, including diet and exercise, should be endorsed.