The article provides a comprehensive overview of the role of nitric oxide (NO) in the health and disease of the respiratory system. NO, initially considered a harmful pollutant, has been identified as a crucial molecule with multiple physiological functions. The production of NO in the respiratory tract is catalyzed by nitric oxide synthase (NOS), which exists in three isoforms: neuronal NOS (nNOS), inducible NOS (iNOS), and endothelial NOS (eNOS). NO has been shown to modulate bronchomotor tone, transcriptional regulation, and immune-inflammatory responses in the lungs. The concentration of exhaled NO is abnormal in various inflammatory airway diseases, making it a potential biomarker for conditions like asthma. Additionally, NO can generate reactive nitrogen species (RNS) under oxidative stress conditions, which may contribute to the development of chronic inflammatory airway diseases. The article also discusses the molecular actions of NO, including its interaction with guanylyl cyclase and the formation of S-nitrosothiols (SNOs), which play important roles in signaling and cellular function. The regulation of NOS and the metabolism of l-arginine are also explored, highlighting the importance of these processes in maintaining NO homeostasis. Finally, the article reviews the physiological and pathophysiological roles of NO in lung development, transcriptional regulation, the inhibitory nonadrenergic noncholinergic (NANC) system, airway smooth muscle relaxation, and airway hyperresponsiveness.The article provides a comprehensive overview of the role of nitric oxide (NO) in the health and disease of the respiratory system. NO, initially considered a harmful pollutant, has been identified as a crucial molecule with multiple physiological functions. The production of NO in the respiratory tract is catalyzed by nitric oxide synthase (NOS), which exists in three isoforms: neuronal NOS (nNOS), inducible NOS (iNOS), and endothelial NOS (eNOS). NO has been shown to modulate bronchomotor tone, transcriptional regulation, and immune-inflammatory responses in the lungs. The concentration of exhaled NO is abnormal in various inflammatory airway diseases, making it a potential biomarker for conditions like asthma. Additionally, NO can generate reactive nitrogen species (RNS) under oxidative stress conditions, which may contribute to the development of chronic inflammatory airway diseases. The article also discusses the molecular actions of NO, including its interaction with guanylyl cyclase and the formation of S-nitrosothiols (SNOs), which play important roles in signaling and cellular function. The regulation of NOS and the metabolism of l-arginine are also explored, highlighting the importance of these processes in maintaining NO homeostasis. Finally, the article reviews the physiological and pathophysiological roles of NO in lung development, transcriptional regulation, the inhibitory nonadrenergic noncholinergic (NANC) system, airway smooth muscle relaxation, and airway hyperresponsiveness.