In smokers with chronic obstructive pulmonary disease (COPD), pathological changes can be found in the central airways, peripheral airways, lung parenchyma and pulmonary arteries. Interestingly, some of these changes can be already present in the lungs of smokers with normal lung function indicating that smoking itself is able to damage the lung even before airflow limitation occurs. The purpose of this paper is to describe the structural changes present in the lungs of smokers with normal lung function and those present in the lungs of smokers with COPD, in an attempt to underline the possible mechanisms contributing to airflow limitation in these patients. In addition we will review the few studies that described the structural changes that occur in severe COPD and those that occur during an exacerbation of the disease. Finally we will address the effect of smoking cessation or anti-inflammatory treatment in an attempt to investigate the potential reversibility of the pathologic lesions characteristic of COPD.