Cigarette smoke contains a large variety of compounds, including many oxidants and free radicals that are capable of initiating or promotes oxidative damage. Also, oxidative damage may result from reactive oxygen species generated by the increased and activated phagocytes following cigarette smoking. In vitro studies are generally supportive of the hypothesis that cigarette smoke can initiate or promote oxidative damage. However, information obtained from in vivo studies is inconclusive. Contrary to expectations, the levels of lipid peroxidation products were found to be decreased or unchanged in the lungs of chronically smoked rats. Metabolic adaptation, such as accumulation of vitamin E in the lung, and increased activities of superoxide dismutase in alveolar macrophages and pulmonary tissues of chronically smoked animals may enable smoked subjects to counteract oxidative stress and to resist further damage to smoke exposure. However, it is also possible that the metabolic adaptation may be secondary to inflammatory response and injury repair process following smoking exposure. More studies are needed to better understand the role of oxidative damage in the etiology of smoking-related disorders.