SUMMARY. The respiratory tract is exposed to a wide variety of exogenous insults as a consequence of the daily inhalation of more than 8,500 litres of air. Recognition and effective host defence against harmful inhaled agents is regulated locally by orchestrated interactions between the humoral and cellular components of innate and adaptive immunity. Recent evidence suggests that the innate immunity has a pivotal role in respiratory antimicrobial defenses by rendering the airway epithelial cells not a passive barrier only, but also an active interface that responds to microbial exposure with the production of a variety of cytokines, chemokines and antimicrobial peptides. The recognition systems of common microbial motifs by airway epithelial cells have recently been described as a diversity of pattern recognition receptors, including the Toll-like receptor family members, which display a certain degree of specificity against a number of pathogen associated molecules. Activation of these receptors regulates not only the killing of microorganisms, but also the recruitment of cells of innate and adaptive immunity, inflammatory and anti-inflammatory responses and, finally, wound repair. The aims of this review are to recapitulate the role of the adaptive immune system in the respiratory tract, highlight the role of innate immunity and describe the new developments in the rapidly evolving area of research into these mechanisms. Pneumon 2007; 20(4):384–394