The burden of chronic obstructive pulmonary disease (COPD) is rising, incurring a major health care burden worldwide. There is no specific therapy other than smoking cessation, which is only partially successful. The condition is recognized to be the result of abnormal control of the inflammatory response to known risk factors, although the exact mechanisms have yet to be identified. However alpha(1)-antitrypsin deficiency represents a human model of all the components of COPD (especially emphysema), and the genetic nature allows family studies of subjects who are well or in the early stages of disease progression. Emphysema distribution has facilitated further understanding of physiologic impairment with particular reference to discordance between FEV(1) and tests of gas transfer. The condition also emphasizes the role of the neutrophil in the inflammatory cascade in both deficiency and usual COPD. Deregulation and resistance of the inflammatory cytokine cascade appears to be a regular feature of usual COPD, and may represent a premature ageing phenotype. Molecular studies provide new insights that may lead to specific therapies to halt progression.