Disruption of the natural equilibria between proteases and their cognate inhibitors is a common feature of inflammatory disease. When this occurs in the lung, the effects can lead to irreversible impairment of pulmonary function. Although protease inhibition has been standard therapy for hereditary emphysema patients for many years, it is only recent studies that have predicted a further and more broad-based role for protease inhibitors in the treatment of respiratory disease. In contrast to current anti-inflammatory respiratory therapeutics, certain small molecule and protein protease inhibitors also have the capacity to inhibit directly the chronic airway remodelling and lung degeneration mediated by uncontrolled proteolytic activity. High efficiency delivery of such agents to the lung, therefore, will not only have a positive impact on lung inflammation, but will also have disease-modifying effects on the progressive loss of lung function caused by chronic degradation of lung tissue.