In the US, lung disease is the number three killer and accounts for one of every six deaths. Furthermore, more than 35 million US populations are now living with a chronic lung disease. Therefore, it is of urgent need to develop novel strategies that can protect against the development and progression of lung disease. Inhalation of air pollutants or environmental toxins induces inflammation and oxidative stress in the lung, resulting in tissue damage with subsequent decline in lung function. Heme oxygenase-1 (HO-1) is a stress response protein, which is highly inducible in response to pathological stimulation. Due to the cumulative effects of HO-1 on heme catabolism and the generation of biologically active downstream products, induction of HO-1 might serve as a protective mechanism against oxidative stress and inflammation-induced injury. Accumulating evidences have indicated a protective function of HO-1 against lung injury. This review highlights the roles of HO-1 in lung disease induced by environmental toxins such as cigarette smoke (CS), silica, and asbestos.