Exhaled nitric oxide (F(E)NO) represents the only exhaled biomarker that has reached clinical practice even in primary care settings, due to the non-invasiveness of its assessment and ease of repeat measurements, even in patients with severe airflow obstruction. While F(E)NO has been suggested as a readily determined biomarker that can aid in the diagnosis and management of asthma, its potential role in pathophysiology of non-pulmonary diseases is less clear and therefore remains to be established. The purpose of the present review is to highlight the current literature investigating the use of F(E)NO in the diagnosis and management of non-pulmonary diseases.