Over the past two decades, eosinophilic esophagitis (EoE) has undergone a remarkable transformation. What used to be a rare, case-reportable condition about which little was known, is now widely recognized as an important cause of upper GI morbidity and the subject of intense research activity. The clinical syndrome has been defined, treatment trials have been performed, and guidelines for diagnosis and management have been published.[1] In parallel with this has been a rapid increase in our understanding of the pathogenesis and genetic basis of EoE.[2–5] While the consensus is that EoE is an allergic/immune-mediated condition in which the eosinophil plays a central role, recent data suggest that ‘non-eosinophil cell types’ play important, and possibly crucial, roles as well. The allergic basis for the disease is based on several lines of evidence. Patients with EoE have a high burden of concomitant atopic conditions,[6–10] allergen-free elemental diets cause nearly universal improvement in symptoms and resolution of eosinophilia,[11, 12] and there is a seasonal variation in EoE, possibly due to aeroallergens.[10, 13–16] Prompted by the review by Zhang and colleagues in this issue of Digestive Diseases and Sciences,[17] this editorial summarizes the role of the eosinophil and several other cell types in the pathogenesis of EoE, including lymphocytes, mast cells, fibroblasts, and epithelial cells. Recognizing and characterizing the role of the non-eosinophil cell types is likely to be central to future advances in the diagnosis and treatment of EoE.