Currently available data indicate a clear and probably causal relationship between long-lasting gastroesophageal reflux disease, the development of long segments with specialized intestinal metaplasia in the distal esophagus and subsequent progression to adenocarcinoma. To a lesser degree, this also appears to be the case for short segments of specialized intestinal metaplasia in the distal esophagus. In contrast, epidemiological data and classic parameters for the diagnosis of gastroesophageal reflux disease do not currently support a causal role of gastroesophageal reflux in the pathogenesis of specialized intestinal metaplasia at the gastric cardia. Despite its high prevalence and malignant potential, many questions about the prevention and management of intestinal metaplasia in the distal esophagus remain unsolved. In patients with chronic gastroesophageal reflux, current modes of medical therapy do not appear to prevent the development of intestinal metaplasia, while effective anti-reflux surgery seems to have a protective effect. Formal studies with adequate follow-up are, however, still lacking. Neither acid-suppression therapy nor anti-reflux surgery, with or without mucosal ablation, can reliably prevent the malignant degeneration of established intestinal metaplasia of the esophagus. Close endoscopic surveillance with extensive biopsies, therefore, remains mandatory in such patients, irrespective of the treatment modality.