The lung has evolved an impressive array of strategies to sense and respond to foreign or dangerous material. This review uses an anatomical approach, from nose to alveoli, to detail our current understanding of these pulmonary defence mechanisms at the cellular and molecular level. Recent advances since the beginning of the 21 st century have been given particular focus. The review initially focuses on individual host defence mechanisms of the upper airways including; the nose, sneeze, cough, the mucociliary apparatus, epithelial cells and dentritic cell network. Then we discuss individual mechanisms of the lower airways including the contribution of macrophages and opsonins to host defence. We then focus attention on the cellular interplay between the mechanisms discussed before finally presenting experimental and clinical evidence of advances that are based on our greater understanding of pulmonary defence mechanisms.