In recent years, part of the scientific community has focused its attention on the involvement of the epithelial-mesenchymal trophic unit (EMTU) in mucosa remodeling, monitoring its role in chronic inflammatory lung diseases. The term EMTU is used to describe the anatomic and functional relationship between the attenuated fibroblast sheath and epithelial tissue, i.e. the signaling between epithelial cells and the underlying fibroblasts, which are in close indirect physical contact with the former. These interactions are important for many airway functions, such as differentiation during lung growth, repair of damaged tissue and regulation of inflammatory response. Several studies have indicated a key role for the EMTU in the processes that influence mucosae remodelling. These processes can be observed in different pathologies, such as asthma or chronic obstructive pulmonary disease (COPD). This review focuses on the primary role of the EMTU in mucosa remodeling, aiming to give a contribution to an issue that, if deepened may lead to more efficient treatments for the handling of chronic respiratory diseases. The close correlation between the reactivation of the EMTU in adult age and the onset of chronic diseases of the respiratory system is now widely accepted by the scientific community. It is therefore of fundamental importance to enhance our knowledge on its reactivation and the processes that lead to tissue remodeling. Pinpointing the key molecular pathways would provide new therapeutic targets for limiting the remodeling processes typical of subjects suffering from different types of airway pathologies.