Barrett's oesophagus is a frequent complication of gastro-oesophageal reflux disease predicting oesophageal adenocarcinoma. The majority of Barrett's patients will not develop cancer, so that specific methods of identification of those at risk are required. Recent molecular studies have identified a selection of candidate biomarkers that need validation in prospective studies. They reflect various changes in cell behaviour during neoplastic progression. The ASPECT trial in the UK aims to establish whether chemoprevention with aspirin and a proton pump inhibitor will reduce adenocarcinoma development and mortality in patients with Barrett's oesophagus. It will also validate biomarkers for progression and clinical response and further study disease pathogenesis.