Internal organs, including the airway, are innervated by neurons of the autonomic and sensory nervous systems. The airway-innervating sensory neurons primarily originate from the vagus nerve, whose cell bodies are found, in rodents, in the jugular and nodose ganglia complex (JNC). About half of these sensory neurons expressed the heat-sensing ion channel TRPV1 and evolved to limit tissue damage by detecting chemical, mechanical, or thermal threats and to initiate protective airway reflexes such as coughing and bronchoconstriction. They also help monitor the host homeostasis by sensing nutrients, pressure, and O levels and help mount airway defenses by controlling immune and goblet cell activity. To better appreciate the scope of the physiological role and pathological contributions of these neurons, we will review gain and loss-of-function approaches geared at controlling the activity of these neurons. We will also present a method to study transcriptomic changes in airway-innervating neurons and a co-culture approach designed to understand how nociceptors modulate immune responses.