Chronic obstructive pulmonary disease (COPD) is a highly prevalent airway disease that causes serious morbidity and mortality. Despite its importance, the cellular and molecular mechanisms that contribute to COPD pathogenesis have only recently been investigated. COPD is characterised by chronic inflammation, and loss of structural integrity throughout the lung from conducting airways, to the alveolar walls. Apoptosis is an active biochemical process, associated with minimal inflammation or disruption of neighbouring tissue. Apoptosis is considered to play an important role in effective repair of an injured airway epithelium, and resolution of inflammation. However, disorders in the apoptotic process, including increased rates of epithelial cell apoptosis or defective clearance of apoptotic cells by neighbouring phagocytes, are associated with tissue injury in several conditions, including liver injury and heart disease. Increasingly, the role of apoptosis in the pathogenesis of COPD is being recognised. Several studies have reported increased apoptosis of airway epithelial cells, and defective clearance of these cells by alveolar macrophages in COPD, although how this relates to the disease process is still largely unknown. Cigarette smoking directly induces apoptosis of airway epithelial cells. However, the increased rate of apoptosis does not appear to diminish with cessation of cigarette smoking. In this regard, factors that relate to perpetuation of the chronic inflammatory response in COPD may also contribute to increased apoptosis in the airways. These include the high level of oxidative stress, release of proteolytic enzymes as a result of increased numbers of neutrophils, cytotoxic T-cells, activation of TNF-α, TGF-β and Fas pathways, and inflammatory responses to colonisation of the airways with bacteria. Understanding the role of apoptosis and phagocytosis in the airways in COPD is likely to lead to novel therapeutic approaches for this extremely common, yet, often neglected disease.