Oxidant/antioxidant imbalance has been implicated in the pathogenesis of several pulmonary diseases, including adult respiratory syndrome, asthma, COPD, cystic fibrosis, cigarette smoke-induced diseases, hyperoxia, environmental and occupational diseases, ischemia/reperfusion injury, idiopathic pulmonary fibrosis, and cancer. Rapid advances in the last few decades have generated a complex and intriguing wealth of knowledge, revealing that in many of these diseases RONS are involved in certain dynamic molecular mechanisms controlling the initiation or promotion of pathological outcome. Evidence from cellular, experimental, and human pulmonary disease studies also indicates that in many instances oxidants are generated in excessive amounts, which overwhelms antioxidant defenses. This results in oxidative stress, which triggers a cascade of molecular events signaling functional and pathological changes in cells, organs, and the whole body. Identification of the specific molecular events that are disproportionately activated by RONS or antioxidants is important for developing antioxidant therapies for the prevention of diseases caused by oxidative stress.