Gastroesophageal reflux disease (GERD) is common. Many patients with recurring or troublesome symptoms are referred for endoscopic examination. Patients seen in secondary care usually have failed OTC or primary care anti-reflux therapy. Acid suppression is the mainstay of healing and maintenance therapy. Increasingly proton pump inhibitors (PPIs) are preferred above H2 receptor antagonists (H2RAs), not only for the more severe end of the GERD spectrum but also for patients with mild degrees of esophagitis. Not all patients respond symptomatically to acid suppression, not even with high dose PPI. Prokinetics are mainly useful in the milder degrees of GERD. It is still not clear whether a particular symptom cluster can be recognized for which prokinetics are especially useful. The concept of "step-up versus step-down" approach remains in need for proper validation. Switching from PPIs to cisapride for "step-down" maintenance appears inadequate in practice. All current therapies have shortcomings; H2RAs insufficiently block meal-stimulated acid secretion; long-term strong acid suppression worsens Helicobacter pylori-associated inflammation in the corpus and may accelerate development of atrophy; PPI-potency is substantially weaker in non-H. pylori infected individuals. Optimization of individualized therapy will require more potent and more precisely targeted motility modulating drugs and superior acid/peptic inhibiting pharmaceuticals.