Nitric oxide (NO) plays role in a great range of important functions in the organism, such as vasodilatation, relaxation of muscles, neurotransmission, neuromediation, and host defense reactions. In the upper airways, nasal cavities and paranasal sinuses are the main sources of this biological mediator. Although the exact role of NO in nasal physiology remains poorly understood, the functions are thought to be host defense, ciliary motility and improved ventilation-perfusion ratio in the lungs by auto-inhalation. Low NO concentrations were reported in certain diseases such as primary ciliary dyskinesia, cystic fibrosis, and acute and chronic maxillary sinusitis whereas high concentrations were detected in upper airway infection, allergic rhinitis and nasal polyposis. Additionally this ubiquitous radical is being implicated in the regulation of cochlear blood flow, sensorineural hearing loss, middle ear effusions, and outer hair cell and vestibular functions. Solid tumors is another area where NO appears to have both tumor-promoting and tumorinhibiting effects. The presence of NO with high levels within the nose and paranasal sinuses makes it reasonable to believe that this pluripotent gas is involved in a variety of physiological as well as pathophysiological events in the airways. Although NO has an ever-increasing role in various areas related to the practice of otolaryngology, further research is required to understand fully the role of NO in the upper airways.