Medical treatment is effective in the majority of patients with gastroesophageal reflux disease (GERD). Lifestyle modifications are often recommended for patients with GERD, although the data supporting lifestyle recommendations are limited. Antacids are often used to treat the symptoms of GERD, but their effect is short-lived. H2-receptor antagonists and proton-pump inhibitors provide more effective options for remission of GERD symptoms and healing of esophagitis. Prokinetic medications (e.g., metoclopramide) have not been proven to help in the control of symptoms. Baclofen, which inhibits transient lower esophageal sphincter relaxations, provide an additional option for patients with persistent symptoms related to GERD; however its use is limited by side effects. Long-term medical therapy for GERD should be tailored to each patient to provide symptomatic control and maintain esophageal mucosal healing.