The respiratory tract is exposed continuously to noxious agents, microbial organisms, particles, and allergens. It has therefore evolved both innate and specific defense mechanisms. The innate host defense mechanisms include components such as collectins, β-defensins, lactoferrin, and complement, all of which have an important role in modulating the immune response. Immune protection of the lungs by specific antibody is reviewed. The airways are protected by alveolar macrophages, neutrophils, and lymphocytes, and their origins, regulation, functions, and antimicrobial activity are summarized. Antimicrobial peptides and immune-modulating peptides are likely to have a significant therapeutic role for infection and inflammation in the respiratory tract.