Eosinophilic esophagitis (EoE) is a chronic clinicopathological entity characterized by large numbers of intraepithelial eosinophils infiltrating the esophageal mucosa, which is not caused by gastroesophageal reflux. This disease has become widely recognized over the past few years and new methods have been developed to reveal its underlying pathophysiological mechanisms. Owing to the high prevalence of food and/or airborne allergen sensitization in EoE patients, the allergic nature of the disease had to be defined, which has certain factors in common with other IgE-dependent entities, such as bronchial asthma or allergic rhinitis. Of these, some cytokines and chemokines previously studied in asthma have also been implicated in molecular mechanisms causing eosinophil-rich esophageal inflammation. However, the role played by IgE in relation to the esophageal eosinophilic infiltrate must be clarified, together with the possible function of mast cells in the inflammatory infiltrate and its activation stimuli. A putative role has also been recently suggested for gastroesophageal reflux in the origin of EoE that should be profoundly analyzed, together with the role of specific genes implicated in other digestive inflammatory disorders. This article reviews recent advances in the immunopathogenesis of EoE, which should also consider other pathways to activate the esophageal mucosal immune system.