Although exposure to tobacco smoke is the primary risk factor for the development of chronic obstructive pulmonary disease (COPD), fewer than 25% of smokers develop the disease and about 15% of COPD-related mortality occurs in never-smokers, suggesting that there are other risk factors involved. These include reduced lung growth during childhood; airway hyperresponsiveness, possibly with an allergic component; asthma; early childhood infection; and noxious environmental agents. Genetic factors also play a role. This article examines the currently available data on COPD susceptibility.