Over the past decade clinicians have witnessed a dramatic rise in the prevalence of eosinophilic gastrointestinal diseases. Diverse symptoms, a broad range of endoscopic findings, and varying histopathologic features pose several questions: Do eosinophils represent an allergic response? What mechanisms drive eosinophils to specific mucosal targets? How do eosinophils affect the gastrointestinal tissues? Recent clinical and basic studies are investigating the pathogenesis of eosinophilic gastrointestinal diseases. This review highlights the literature concerning the mechanisms that govern these diseases, with a specific focus on diseases of gastrointestinal columnar epithelia (eosinophilic gastroenteritis and eosinophilic colitis). The roles of specific chemokines, such as eotaxin, and the data supporting the involvement of eosinophil granule proteins in disease states, are discussed.