The neurobiology of dyspnea is varied and complex, but there is little doubt that vagal nerves within the airways are capable of causing or modulating some dyspneic sensations, especially those associated with inflammatory airway diseases. A major contributor to the dyspnea associated with inflammatory airway disease is explained by airway narrowing and increases in the resistance to airflow. The autonomic (parasympathetic) airway nerves directly contribute to this by regulating bronchial smooth muscle tone and mucus secretion. In addition, a component of the information reaching the brainstem via airway mechanosensing and nociceptive afferent nerves likely contributes to the overall sensations of breathing. The airway narrowing can lead to activation of low threshold mechanosensitive stretch receptors, and vagal and spinal C-fibers as well as some rapidly adapting stretch receptor in the airways that are directly activated by various aspects of the inflammatory response. Inflammatory mediators can induce long lasting changes in afferent nerve activity by modulating the expression of key genes. The net effect of the increase in afferent traffic to the brainstem modulates synaptic efficacy at the second-order neurons via various mechanisms collectively referred to as central sensitization. Many studies have shown that stimuli that activate bronchopulmonary afferent nerves can lead to dyspnea in healthy subjects. A logical extension of the basic research on inflammation and sensory nerve function is that the role of vagal sensory nerve in causing or shaping dyspneic sensations will be exaggerated in those suffering from inflammatory airway disease.