Eosinophils are commonly detected in normal mucosal biopsies from all sites within the gastrointestinal tract where they are dispersed in the lamina propria and, to a lesser extent, in the epithelium. The distinction between the upper limit of normal and abnormally increased tissue eosinophils is not well defined. However, eosinophils that infiltrate the epithelium in more than occasional numbers, coalesce to form aggregates, or show extensive degranulation are always abnormal and raise a broad differential diagnosis. Although the differential diagnosis of purely eosinophilic inflammation is largely limited to hypersensitivity reactions and some infections, they are increased in several gastrointestinal conditions, including gastroesophageal reflux disease, autoimmune gastritis, infections, drug reactions, inflammatory bowel disease, radiation enteritis, and collagen vascular disease. These disorders feature eosinophils as one component of a mixed inflammatory infiltrate that can, in some instances, be prominent enough to cause diagnostic confusion. The purpose of this review is to discuss the normal distribution of eosinophils in the gastrointestinal tract and the differential diagnosis of inflammatory conditions that feature prominent eosinophilia.