Cystic fibrosis (CF) is characterized by chronic airway infection and inflammation, which accounts for most morbidity and deaths. Exhaled nitric oxide (NO), elevated in most inflammatory lung diseases, is decreased in CF, suggesting decreased formation, increased metabolism or loss of NO. The nitrogen oxide metabolism in CF airways is complex and not yet fully understood. In this article we will summarize current understanding of the origin and function of NO in (patho)physiological processes in the lung of normal subjects and CF patients, possible explanations for and consequences of reduced NO concentrations in CF and possible therapetic strategies for treatment of CF patients.