©2018 American Association for Cancer Research. Despite esophageal adenocarcinoma (EAC) being the most widespread among gastrointestinal cancers, with an 11-fold increase in the risk of cancer for patients with Barrett esophagus (BE), its prognosis is still poor. There is a critical need to better perceive the biology of cancer progression and identification of specific targets that are the hallmark of BE's progression. This review explores the established animal models of BE, including genetic, surgical and nonsurgical approaches, potential chemoprevention targets, and the reasoning behind their applications to prevent Barrett-related EAC. The key methodological features in the design feasibility of relevant studies are also discussed.