<p>Gastroesophageal reflux disease (GERD) is one of the most common gastrointestinal diseases. In clinical practice, when typical symptoms are present, initial diagnostic imaging can often be avoided and a trial treatment can be initiated. In the absence of response or if interventional therapy is planned, further diagnostic testing is required. In addition to endoscopy with histology, particularly functional diagnostics using 24 h impedance–pH testing is the gold standard and high-resolution manometry is also indicated to primarily exclude motility disorders. Particularly challenging is the assessment of proton pump inhibitor (PPI)-refractory symptoms. The focus here is on excluding alternative etiologies, optimizing acid-suppressing therapy, and conducting structured functional diagnostics. The resulting findings enable targeted, individualized treatment decision-making.</p>