Gastroesophageal reflux disease (GERD) is one of the most common complaints in general medical practice. Symptoms of GERD have a high prevalence, which greatly affects health economics and patient health-related quality of life (HRQOL). The majority of patients who present with reflux symptoms lack esophageal mucosal injury and thus have symptomatic GERD. There appear to be no differences in either symptoms or HRQOL measures between patients with or without positive endoscopy. Although most pharmacoeconomic and HRQOL assessments have focused on erosive GERD patients, available data suggest that the impact of symptomatic GERD on HRQOL is significant and equivalent to that associated with erosive disease. Proton pump inhibitors (PPIs) improve HRQOL to a greater extent than either histamine(2)-receptor antagonists or prokinetics in patients with GERD, with PPI-based step-down or "on-demand" strategies yielding the most cost-effective benefit to health. Additional HRQOL and outcomes research focused on patients with symptomatic GERD, ideally using disease-specific assessment tools, is needed. Furthermore, these management strategies must be implemented in real world settings to validate their effectiveness and firmly establish claims of reduced need for diagnostic testing and decreased direct medical costs.