This article seeks to provide updated information on the pathogenesis of Barrett’s esophagus (BE) including the possible cellular origins of esophageal columnar cells and the impact of chronic esophageal inflammation. Other considerations include clinical exposures and the importance of risk factor modifications such as weight loss and tobacco cessation. The article summarizes genetic risk factors in the pathogenesis of BE and discusses how familial risk and exposures are considered in current guidelines to identify those who may benefit from BE screening. Finally, insights gleaned from postablative therapy are integrated into this article for both clinical providers and researchers.