Eosinophilic gastrointestinal diseases (EGIDs) are characterized by a wide variety of gastrointestinal symptoms that occur in conjunction with increased numbers of eosinophils in intestinal tissues. With the precise role or roles of eosinophils in gastrointestinal dysfunction incompletely understood, this subject remains an area of intense investigation. Most studies suggest that the intimate anatomic association of eosinophils with the intestinal epithelium implicates participation in the pathophysiology of EGIDs. This article reviews the limited evidence suggesting that the epithelium and eosinophils interact in the gastrointestinal tract and in other organ systems and describes how the epithelium and eosinophils might participate in gastrointestinal inflammatory diseases.