The rate of oesophageal adenocarcinoma is increasing in the western world and has a poor prognosis mainly because individuals present at a late stage. Attempts to intervene at an early stage of tumour progression have not proven cost effective, although lesions identified during surveillance programmes have a better prognosis. As a consequence, there has been renewed interest in strategies that might prevent the precursor lesion Barrett's oesophagus. Furthermore, there is an improved understanding of genetic and environmental interactions necessary for the clonal expansion and propagation of metaplastic premalignant lesions. Clearly, three mechanisms promote cancer progression--inheritance of germ-line mutations or polymorphisms, sporadic mutagenesis, and local epigenetic alterations. Locally produced cytokines and bile acids in the refluxate create a microenvironment that sets the scene for metaplastic transformation of the oesophageal epithelium, mainly by directly affecting metaplastic stem cells.