Eosinophilic esophagitis (EoE) now represents a commonly recognized disorder among both pediatric and adult patients presenting to allergy and gastroenterology clinics throughout the world. The consequences of this localized and eosinophil-predominant inflammation of the esophagus can have an outsized and profound systemic and emotional impact for patients and their families. Unlike gastroesophageal reflux disease (GERD), whose symptoms closely overlap with those of EoE, EoE represents a primarily antigen-driven disorder whose symptoms and pathology are therapeutically mitigated with either long-term dietary control or chronic steroid therapies, rather than the acid-suppressive medications that are the mainstay of GERD treatment. Beyond the dissimilarities in their responses to treatment, these disorders are distinct in their gene expression profiles, heredity, genetic underpinning, and linkage with atopy. The antigen-driven nature of EoE has been reinforced by the remarkable impact of therapies utilizing elemental formulas to control the disease as well as a number of reports linking aeroallergens to seasonal worsening of disease.