Alveolar macrophages play a critical role as orchestrators of inflammation in chronic obstructive pulmonary disease (COPD). The numbers of alveolar macrophages are markedly increased in the lungs of patients with COPD as a result of increased recruitment, proliferation and survival. Alveolar macrophages secrete many inflammatory mediators, oxidants, proteins and proteinases in response to cigarette smoke extract and other stimuli. In COPD there is amplified secretion of these inflammatory products which may be related to defective histone deacetylase-2, which may also account for the steroid resistance of these cells in COPD patients. There are several novel therapeutic strategies targeted at macrophages.