Metaplasia (or transdifferentiation) is defined as the transformation of one tissue type to another. Clues to the molecular mechanisms that control the development of metaplasia are implied from knowledge of the transcription factors that specify tissue identity during normal embryonic development. Barrett's metaplasia describes the development of a columnar/intestinal phenotype in the squamous oesophageal epithelium and is the major risk factor for oesophageal adenocarcinoma. This particular type of cancer has a rapidly rising incidence and a dismal prognosis. The homoeotic transcription factor Cdx2 (Caudal-type homeobox 2) has been implicated as a master switch gene for intestine and therefore for Barrett's metaplasia. Normally, Cdx2 expression is restricted to the epithelium of the small and large intestine. Loss of Cdx2 function, or conditional deletion in the intestine, results in replacement of intestinal cells with a stratified squamous phenotype. In addition, Cdx2 is sufficient to provoke intestinal metaplasia in the stomach. In the present paper, we review the evidence for the role of Cdx2 in the development of Barrett's metaplasia.