Barrett's esophagus (BE) is an intestinal-like columnar metaplasia that replaces the normal stratified squamous epithelium in the distal esophagus. Clinically, BE is an important entity as it is the only established precursor to esophageal adenocarcinoma (EAC), a disease with an extremely poor prognosis and an incidence that is rising faster than any other solid cancer worldwide. Therefore, because of the increasing burden of EAC, there has been much research aimed at understanding the development of BE, in order to develop new ways to combat this disease. BE arises as a consequence of chronic reflux. Whilst the central role of reflux in driving the development of BE has been well established, the cellular and molecular mechanisms that accompany this process remain to be fully elucidated. Understanding the drivers at a fundamental level is crucial for the rational design of novel therapeutic strategies aimed at preventing the progression of, or even reversing, BE. In this article we review some of the recent advances that have contributed to our understanding of BE pathogenesis, including new findings on the possible cellular origins of the metaplastic epithelium, and the morphogens and transcription factors that putatively drive the conversion of the squamous epithelium to an intestinal-like columnar epithelium.