The “Unified Airway” is a conceptualized organ comprising structures in both the upper and lower airways. This concept recognizes that many aspects of respiratory health are not organ-dependent. What effects the nose and sinuses can also impact asthma. Many conditions such as aspirin-exacerbated respiratory disease, cystic fibrosis, and eosinophilic granulomatosis with polyangiitis are almost always associated with inflammation of the entire respiratory tract. This chapter focuses on the various mechanisms that can influence the airway in a unified manner. This review addresses aspects of allergic responses in the airway, the influence of the microbiome, the role of the bitter taste receptor, and innate immune activation. The larynx, sometimes overlooked in discussions of the unified airway is reviewed here, particularly regarding cough. All these areas have some unique therapeutic considerations which are also briefly reviewed. It is important that all physicians who treat airway conditions become familiar with the concept of the unified airway.