A multitude of overlapping defenses has evolved to help combat the inventiveness of pathogens seeking to invade us, and because the lung is the most common primary route of infection, it is in the lung that the most varied responses are seen. This article focuses on recent research, particularly in innate immunity, and gives a general overview of the defense systems so far identified. Of particular interest is the markedly increased understanding of the role of small molecules such as defensins, cathelicidins, and collectins. Areas in which abnormalities may be relevant to patients with bronchiectasis are highlighted.