Superoxide formation in pulmonary tissue is modulated by cytokines, PO2, shear force, and disease states, and can be stimulated by drugs. Superoxide has diverse actions on pulmonary cells, including smooth muscle contraction, interaction with redox enzymes, cell proliferation, and gene transcription. In the lungs, there is an impressive array of specific defence mechanisms that destroy superoxide, especially superoxide dismutase (SOD) and metallothionein. Superoxide formation is increased in hyperoxia (e.g., oxygen therapy); however, superoxide-forming enzymes also can be up-regulated in hypoxia. Superoxide has been implicated in acute respiratory distress syndrome, lung ischaemia-reperfusion injury, and lung transplantation. Novel approaches to therapy have been explored, including SOD gene therapy and SOD targeting to the lung. In the future, new drugs interacting with superoxide may provide significant advances in the treatment of lung diseases.