Irritable Bowel Syndrome (IBS) is a chronic disorder with symptoms that range in intensity from mild and infrequent to severe and continuous. Similarly the impact of IBS on Quality of Life (QOL) measures can range from very small to disabling. In a very simple model one might expect a change in symptom intensity or frequency to be reflected in a similar change in QOL. However, a variety of other factors may alter this straightforward and unidirectional relationship between symptomatic treatment and QOL improvement. This paper presents several classes of these potential moderator variables in QOL outcome in IBS, as well as specific models of symptom, moderator, QOL relationships that can be investigated in future research. An illustrative example of a regression approach to analysis of psychosocial moderator variables indicates both psychosocial measures, and symptom severity, independently contribute to the prediction of QOL in IBS.