Gastro-oesophageal reflux disease (GORD) is associated with a broad array of symptoms that may be typical or atypical of the disease and that may be accompanied by erosive oesophagitis. Symptom scales that have historically been employed to assess response to treatment in GORD clinical trials do not typically account for the heterogeneous, episodic nature of GORD and the poor correlation between patients’ and physicians’ assessment of symptoms. The ReQuest™ questionnaire permits self-assessment of changes on a broad range of GORD-related symptoms on a daily basis and in combination with the Los Angeles (LA)-classification (ReQuest™/LA-classification) to assess complete remission of GORD. Pantoprazole and esomeprazole are two of the newer proton pump inhibitors and are the first to be systematically reviewed using the ReQuest™ questionnaire. Results from recent head-to-head trials have shown pantoprazole and esomeprazole to be highly and equally effective treatments for (i) rapid and sustained relief of ReQuest™-assessed GORD-related symptoms in patients with non-erosive GORD or endoscopically confirmed erosive GORD, and (ii) achieving a combined outcome comprising endoscopically confirmed healing and ReQuest™-assessed symptom relief in patients with erosive GORD. There is some preliminary evidence to suggest that pantoprazole may be the better choice of treatment in terms of its potential to maintain control of symptoms in patients for whom night-time symptoms are a concern and if taken as on-demand rather than continuous maintenance therapy.