In the human respiratory tract, the main production sites of exhaled nitric oxide (NO) are the nose and paranasal sinuses. In the upper airways, NO has been suggested to be involved at different levels with regulatory, protective, defensive or deleterious effects. Therefore, we review some aspects of the origin, metabolism, and functions of NO in the upper airways, together with the role of NO in some upper airways inflammatory diseases. Furthermore, we discuss the recent improvements in nasal NO measurements, which may be useful to better characterize the involvement of the NO produced by nose and paranasal sinuses in upper airways inflammatory diseases such as allergic rhinitis, nasal polyposis, sinusitis, primary ciliary dyskinesia, and cystic fibrosis.