Inflammatory bowel disease involves an interaction between genetic susceptibility, a host mucosal immune response and the enteric flora. However, the relapsing and remitting course underlines the importance of other modifiers, such as psychological stress. Doctors and patients share the view that stress plays a role in the initiation and perpetuation of disease. Levels of chronic perceived stress have been shown to correlate with symptom relapse and mucosal appearance, and stress management therapy has been shown to be beneficial. Animal models provide further evidence that stress may play a role in disease initiation and reactivation. Elucidation of the gut-brain-immune axis has provided insight into the mechanisms by which stress may result in gut inflammation. Stress can alter intestinal physiological function. Stress can increase gut permeability, increase ion secretion by a mechanism involving neural stimulation or mast cells, increase mucin release and deplete goblet cells. Stress causes parasympathetic activation via a mechanism involving corticotropin releasing factor, ultimately affecting mucosal mast cells. Stress also results in increased bacterial adherence and decreased luminal lactobacilli. As a result of all these changes luminal antigens may gain access to the epithelium, causing inflammation.