For a long time heartburn was not considered a symptom for serious illness. By now, however, it is accepted that the incidence of secondary carcinoma of the esophagus caused by chronic GERD has increased dramatically since the nineteen-seventies. Mechanisms leading to GERD are complex and its incidence is not necessarily pathological. However pathological reflux in the lower esophagus (pH lower than 4 in 6 % of 24 hours), caused by decreased sphinctertonus, impaired peristalsis and clearance of the esophagus, may lead to complications. Helicobacter pylori may play a key role in GERD. There is strong evidence for a protective effect of Hp-infection in the development of GERD. In pangastritis, caused by Hp-infection, gastric acid production is inhibited resulting in a reduction of stomach-acid-concentration. This may be caused by either the chronic infection itself and the resulting atrophy of the stomach-mucosa, by the ammonia-producing HP-bacteria, or an increase in acid re-absorbtion of gastric epithelium. Laryngopharyngeal reflux (LPR) often results in atypical manifestations with oral, pharyngeal, laryngeal, and pulmonary disorders. Laryngopharyngeal reflux is known to contribute to posterior acid laryngitis and laryngeal contact ulceration or granuloma formation, laryngeal cancer, chronic hoarseness, pharyngitis, asthma, pneumonia, nocturnal choking, and dental diseases. Today, PPI are the medication of choice in both acute and long-term (prophylactic) therapy of GERD. The so called "step-up-strategy" of medication is no longer recommended. Here, patients were first treated with antacids, then prokinetics followed by H2-blockers and finally low-dose PPI. Only in the case of persisting symptoms medication was further increased to high-dose PPI therapy. In the past this increase in medication lead to a prolonged healing process and consequently to higher medication costs. Studies have shown that a "step-down"-therapy, beginning with high dose PPI, is highly preferable, since it is much more effective. Depending on the degree of the symptoms, however, medication may also be applied "on-demand". The BfArM has approved this kind of medication application only for Esomeprazol (Nexium mups 20 mg).