Publisher Summary This chapter focuses on the properties and role of gastrointestinal eosinophils in health and disease. Eosinophils are multifunctional proinflammatory leukocytes implicated in the pathogenesis of numerous inflammatory processes, especially allergic disorders. In addition, it is recently recognized that eosinophils may have a physiological role in organ morphogenesis (for example—postgestational mammary gland development). Eosinophils express numerous receptors (for cytokines, immunoglobulin, and complement proteins) that when engaged lead to eosinophil activation, resulting in several processes, including the release of toxic secondary granule Proteins. Understanding the processes that regulate eosinophil trafficking in the gastrointestinal tract is not only important in clinical diseases but may also have important implications in further understanding the role of eosinophils in innate immune responses and in immune surveillance of healthy tissues. The accumulation of eosinophils in the gastrointestinal tract in diverse medical diseases is often associated with serious medical consequences (for example—weight loss, malabsorption, architectural changes of the intestine such as blunting of the villi), but the role of eosinophils in the pathogenesis of these diseases has been debated. Recent progress in experimental modeling of eosinophil-associated gastrointestinal diseases is instrumental in determining that gastrointestinal eosinophils can be directly increased by mucosal allergen challenge.