Barrett's esophagus is the chief risk factor for esophageal adenocarcinoma. Reflux of gastric acid has long been related to the development of esophagitis and Barrett's esophagus, but the role of duodenal contents is controversial. We review the literature on the role of duodenal contents in the development of esophagitis, Barrett's esophagus and adenocarcinoma in addition to the role of acid suppressant therapy in the development or prevention of these changes. A computer-based search of the literature using the terms "Bilirubin, Barrett, Bile Reflux, duodeno-gastric reflux and oesophagus/esophagus" was performed. The role of bile and other constituents of duodenal refluxate were examined. Techniques for identifying nonacid reflux were also reviewed, as were the role of pH, medication and surgery in modulating disease severity. Complicated Barrett's esophagus is associated with increased exposure to gastric and duodenal refluxate. Biological effect of bile acids depends on the conjugation status, the pH of the milieu and the pKa of bile acids. While Proton Pump Inhibitors reduce the levels of DGER, they also produce changes in gastric and lower esophageal pH that activate different bile acids at different pH levels resulting in unexpected injury. Conjugated bile acids are harmful in acidic environment while unconjugated bile acids are harmful at neutral pH environment. An overlap of toxicity among conjugated and unconjugated bile acids occurs between strongly acidic and neutral pH levels. Normalisation of gastric and duodenal refluxate should ideally be the goal of treatment.