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Pharmacological treatment of gastroesophageal reflux (GER) disease is mostly based on acid control. However, different molecules have been proposed both for patients with persisting symptoms and to limit adverse effects of proton pump inhibitors (PPI). This paper focuses on other acid inhibitors, alginate, prokinetics, drug acting on lower esophageal sphincter and esophageal hypersensitivity. Mechanism of action, indications, efficacy, limits and recent advances are reported. Pediatric data and possible adverse effects are also considered.