Besides the skin, the respiratory tract is the major organ that is continuously exposed to the external environment. As such, this organ is continuously challenged by a wide variety of exogenous hazards (gaseous air pollutants, cigarette smoke, exhaust particles, allergens, pathogens, etc.) that threaten normal lung function. To assure maintainance of adequate lung function and to minimize the occurrence of continuous infections, the respiratory tract is endowed with an exhaustive and unique network of innate defense systems. Perhaps most importantly, mucociliary clearance mechanisms are essential for the removal of inhaled pathogenic particles, that would otherwise provoke chronic inflammatory responses. This mucocilliary clearance pathway is supported by the secretion of mucins that trap inhaled particles or pathogens and allow their efficient removal. However, these airway secretions also contain a number of peptides and proteins that directly kill or inhibit pathogens (defensins, lysozyme, cathelicidin, lactoferrin, lactoperoxidase), or modulate inflammatory responses. Finally, several cellular components, involving epithelial cells and alveolar macrophages as well as recruited professional phagocytic cells such as neutrophils, initiate or coordinate additional host responses to infection and provide effector functions against pathogens.