Detailed investigations and objective measurements in patients with symptoms of gastro-oesophageal reflux should be performed with the intent of making the correct diagnosis, thus enabling choice of appropriate therapy. Establishing the most effective therapy is particularly important in adults who do not respond to standard treatment and in children. The use of PPIs for suspected GERD has increased substantially over the past decade, providing great relief in patients with acid-related symptoms, but also leading to adverse effects and a considerable economic burden. Adults with functional heartburn do not benefit from PPIs, while prolonged PPI use in patients with extraoesophageal symptoms remains a controversial area. Moreover, PPIs are not indicated in infants with GERD unless symptoms are proven to be acid-related. With regard to antireflux surgery, patients must be carefully selected to avoid the need for ongoing PPI treatment postoperatively. Correct diagnosis and phenotyping of patients with symptoms attributed to gastro-oesophageal reflux through detailed investigations is therefore imperative, leading to improved patient outcomes and rationalized use of available treatment options. In this Review, we outline currently available diagnostic tests and discuss approaches to limit any unnecessary medical or surgical interventions.