Excessive reflux of bile into the stomach or esophagus has been associated with a variety of benign and malignant foregut disorders. The interaction of gastric acid with bile acids and the development of mucosal damage has been studied extensively in in vitro and in vivo animal models. These studies show that soluble bile acids can enter mucosal cells when in their non-ionized lipophilic form, accumulate there up to eight times the luminal concentration, and thus cause injuries to cell membranes and tight junctions. Entrance of mucosal cells and accumulation are pH-dependent and more pronounced at acidic pH ranges. The noxious effect of bile on intestinal mucosa is thus related not only to the concentration of luminal bile acids but also to the pH and the mucosal exposure time. Due to the lack of objective and accurate tests to quantitate reflux of bile acids in vivo over prolonged periods of time, the concept of bile reflux as a pathogenic factor in the clinical situation has been controversial. Recent studies indicate that intraluminal bilirubin can be used as a reliable marker of bile reflux into the stomach or esophagus. Combined 24-hour monitoring of intraluminal pH and bilirubin with the newly-developed Bilitec system, despite some system-inherent shortcomings, therefore has the potential to clarify the interactions between bile reflux, mucosal injury and gastroesophageal carcinogenesis.