Airways are exposed to high levels of environmental oxidants, yet they also have enriched extracellular antioxidants. Airways disease such as asthma, cystic fibrosis, and chronic obstructive pulmonary disease have evidence of increased oxidative stress, suggesting that reactive oxygen and nitrogen species may overwhelm antioxidant defenses in airway diseases. Extracellular superoxide dismutase is abundant in pulmonary tissues and protects the lung from increased oxidative stress; however, its role in asthma and other airway diseases has not been fully elucidated. Proteolytic processing of extracellular superoxide dismutase decreases its affinity for the extracellular matrix and may be a mechanism to regulate its distribution during conditions of inflammation or oxidative stress.