© 2005 by Taylor & Francis Group, LLC. This chapter covers reactive oxygen and nitrogen species and their importance in inflammatory lung injury. As described in prior chapters, the pathophysiology of lung injury is multifaceted, and includes the elaboration of reactive oxygen and nitrogen species by inflammatory cells. Reactive oxygen and nitrogen species are of considerable importance in innate immunity and cellular regulation, but their release also results in collateral damage to lung tissue that can ultimately compromise both gas exchange and host defense. For example, reactive nitrogen species (RNS) produced by macrophages in the presence of physiologic CO2 tensions can induce nitration of surfactant protein A (SP-A) and compromise its ability to act as a collectin during host defense. Endogenous reactive oxygen and nitro- gen species can also cause cell and tissue injury by a variety of other mechanisms. In addition, exogenous reactive oxygen and nitrogen species can also be involved in generating lung injury (e.g., from environmental exposure to hyperoxia, ozone, nitric oxide, or related gases). This chapter reviews the fundamental chemistry of reactive oxygen and nitrogen species, as well as their positive and negative biological effects. Emphasis is on the roles of reactive species in acute injury and pulmonary disease based on basic science and clinical perspectives. Pulmonary antioxidant defenses against reactive oxygen and nitrogen species are also discussed. Therapeutic applica- tions targeting oxidant-related pathophysiology are noted, with further details on antioxidant therapies for lung injury given later in Chapter 16.