The past decade has been marked by a considerable increase in the number of patients with gastroesophageal reflux disease and gastroduodenal ulcer who show an inadequate response to proton pump inhibitor (PPI) therapy. At the present time, most of the causes diminishing the response have been elucidated. Unfortunately, they cannot always be eliminated by drug therapy; nonetheless, rabeprazole has a number of advantages over other PPIs. The major causes of an inadequate response to PPI therapy are low treatment motivation; nocturnal gastric acid breakthroughs; genetically determined CYP polymorphism; chiefly nighttime symptoms of gastroesophageal reflux disease; non-acid refluxes; hypersensitive esophagus; overweight and obesity.