Chronic obstructive pulmonary disease (COPD) is characterised by progressive diminution of pulmonary function with minimal reversibility. The initially organ-related symptoms gradually involve secondary organs and end-stage COPD can be considered a systemic disease. The most important cause of COPD is tobacco smoking. In recent years there has been increasing focus on the pathophysiological events leading to COPD, and oxidative stress has been suggested as one of the major pathophysiological factors. Clinical studies indicate a causal association between tobacco smoking, oxidative stress, increased inflammatory response, and destruction of lung parenchyma. This article reviews the clinical literature on oxidative stress as a pre-inflammatory state, leading to COPD in susceptible smokers.