Chronic constipation requiring surgical ablation for intractability is often a frustrating condition from the pathologist's point of view. In fact, limiting the histological examination to only hematoxylin-eosin staining usually yields only the information that there are no abnormalities. By employing some simple and widely available immunohistochemical methods, discussed in this review, it is possible to gather data that may help in explaining the pathophysiological basis of constipation in these patients.