Extra‐esophageal reflux is suspected to cause a wide range of clinical symptoms in the upper airways. Diagnosis and treatment has focused on acid, but realization of the role of nonacid reflux has resulted in research investigating the use of pepsin as a biomarker for gastric reflux and aspiration. Pepsin analysis can complement the use of questionnaires and office‐based diagnosis and lessen the dependency on invasive and expensive diagnostic tests. Furthermore, pepsin as a first‐line diagnostic biomarker has been shown to improve the accuracy of reflux diagnosis. In addition to its use as a diagnostic biomarker, pepsin has been shown to cause inflammation independent of the pH of the refluxate and thus despite acid suppression therapy. Research is ongoing to develop new therapies for airway reflux that specifically target pepsin. Diagnosis and treatment of extra‐esophageal reflux (EER), which is suspected of causing a range of symptoms in the upper airways, has focused on acid. However, realization of the role of nonacid reflux has resulted in research investigating the use of pepsin as a biomarker for gastric reflux and aspiration. Pepsin analysis improves the accuracy of reflux diagnosis and reduces the need for invasive and expensive diagnostic tests.