Gastro-oesophageal reflux disease is a multifaceted and multifactorial disorder which results from the reflux of gastric contents into the oesophagus. Animal studies suggest that synergism between acid and pepsin and conjugated bile acids have the greatest damaging potential for oesophageal mucosa, although unconjugated bile acids may be caustic at more neutral pH. Human studies are compatible with a synergistic action between acid and duodenogastric reflux in inducing lesions. During prolonged monitoring studies, typical gastro-oesophageal reflux symptoms are more related to acid reflux events than to non-acid reflux events. However, symptoms that persist during acid suppressive therapy are often related to non-acid reflux events. The therapeutic options for the non-acid component of the refluxate, including acid suppression, prokinetics, baclofen, surgery and mucosal protective agents like alginates, are discussed.