Eosinophilic esophagitis (EoE) has been increasingly recognized as a unique clinicopathological entity over the past two decades. In this short time, the mechanisms of a complex disease have begun to emerge. Patient studies suggest that EoE is an immunologic disease related to atopy. At the cellular level, eosinophils, mast cells, and B and T lymphocytes are increased in the esophageal mucosa in a patchy distribution throughout the length of the esophagus. Laboratory investigations have implicated aeroallergens, food allergens, and a unique T helper type 2 cytokine profile. EoE appears to be an antigen-driven hypersensitivity reaction characterized by a mixed IgE-dependent/delayed-type reaction and a distinct cascade of cytokines and growth factors. The causative events that lead to EoE in humans remain unknown.