The scientific basis and the clinical application of mAb therapies that target specific immunologic pathways for eosinophilic gastrointestinal diseases are areas of active interest. There is a growing recognition of a subset of patients with eosinophilic esophagitis whose disease does not respond well to topical steroids or elimination diets. In addition, long-term use of corticosteroids presents possible risks that are currently being evaluated. Systemic therapy with a biologic agent offers potential advantages as a global approach that could limit the need for multiple, locally active medical therapies and allergen avoidance. The identification of novel biologic strategies is ongoing, and the recent validation of instruments and outcome measures to assess disease activity has proved essential in demonstrating efficacy. Studies using biologics that target IL-13 pathways in the treatment of eosinophilic esophagitis have demonstrated substantial promise.