The respiratory tract presents a large and potentially vulnerable surface to inhaled microbes. It is coated by a thin layer of secretions generated by airway epithelial cells, submucosal glands, resident and recruited phagocytes (neutrophils, eosinophils, monocytes, and macrophages) and alveolar epithelial cells, as well as substances that enter from blood plasma. More than 80 years ago, Alexander Fleming observed that respiratory secretions have microbicidal and microbistatic properties. He described the activity of lysozyme, one of the principal polypeptides of these secretions. Since then, a number of additional antimicrobial components have been identified, and there is increasing insight into their complex interactions. This review is an update of my previous summary of this area.