The incidence of oesophageal adenocarcinoma is increasing rapidly in Western populations. Gastro-oesophageal reflux disease is a strong risk factor for both this tumour and the pre-cancerous lesion Barrett's oesophagus, but the underlying disease mechanisms remain unclear. Developing a better understanding of the aetiology and pathogenesis of Barrett's oesophagus, including the induction of DNA damage and genetic alterations, might provide opportunities for improved management of individuals with this disease. This could include a better rationale for screening and surveillance programmes, as well as targeted intervention strategies.