Gastroesophageal reflux disease (GERD) presents symptomatically and the main aim of treatment is to reduce or abolish these reflux-related symptoms. Objective tests such as endoscopy, esophageal pH monitoring, and esophageal histology, identify a high proportion of patients who have reflux-related esophageal injury but they identify a smaller proportion of patients with “typical” reflux symptoms and, probably, a yet smaller proportion with atypical, chest pain symptoms. The usefulness of objective tests for determining the role of gastroesophageal reflux in the etiology of extraesophageal respiratory, oropharyngeal and otorhinologic syndromes are even more limited. Symptom assessment is, therefore, crucial for the management of reflux disease. However, the symptomatic manifestations of GERD are protean and, although typical symptoms of heartburn and regurgitation are associated with GERD in a high proportion of individuals, there is no single symptom or combination of symptoms that is diagnostic of GERD, particularly when the esophageal and extraesophageal syndromes are considered. Symptom-based questionnaires developed for the diagnosis of GERD are not, therefore, adequate for the identification of all individuals with GERD although their diagnostic accuracy can be improved by combining them with other diagnostic tests and applying, for example, latent class analysis or Bayesian analysis. Symptom assessment is also crucial in evaluating the effect of therapy in individuals who have a diagnosis, confirmed or presumptive, of GERD. In clinical practice, treatment-induced symptom resolution is generally associated with an improvement in the patient's quality of life and is predictive of an improvement in esophageal injury syndromes; in clinical trials, it is necessary to know that an improvement in symptoms is actually indicative of an improvement in the manifestations of GERD. The need for a validated, symptom-based, evaluative instrument to assess GERD symptoms and their response to therapy has been addressed by the development of a new tool—the ReQuest questionnaire. ReQuest has now been validated in patients with erosive esophagitis, patients with nonerosive reflux disease, and in individuals who do not have reflux disease and it provides an instrument that may be used in clinical research and regulatory studies to document treatment efficacy. In the future, it may also be combined with empiric acid suppression therapy, for example with a proton pump inhibitor, to provide a GERD diagnosis ex juvantibus, without the need for supplementary expensive or invasive investigations.