Both subjective and objective clinical endpoints were used to assess the therapeutic outcome in gastroesophageal reflux disease (GERD). Symptoms could have been used as an indicator of clinical effectiveness, in conjunction with normalization of objective measures such as esophageal acid exposure and inflammation. However, GERD therapeutic trials have shown that many patients who were asymptomatic through medical, surgical, or endoscopic therapy still had abnormal esophageal acid exposure and erosive esophagitis. The opposite has also been proven in medical testing, where patients remained ill despite improved esophageal acid exposure and complete resolution of esophageal inflammation. Furthermore, there was no data to suggest that the symptom response to antireflux therapy necessitates complete esophageal mucosal healing or normalization of esophageal acid exposure. This implied that to translate into meaningful changes in GERD patients’ symptoms and health-related quality of life, a certain degree of improvement in objective criteria was required. It supported the need to reconsider the prevalent “hard” clinical endpoints in GERD investigations.