The rising prevalence of Barrett's esophagus and Barrett's associated adenocarcinoma in the Western world has stimulated increasing interest in this disease. This has resulted in a plethora of articles concerning its molecular biology, but the tumor suppressor gene, p27, has received little attention. In this article, we review the literature concerning the role of p27 in Barrett's esophagus and its malignant transformation, and we evaluate its possible role as an important clinical biomarker, as well as potential chemopreventive clinical agents aimed at substituting its antitumoral activity.