The protease pathogenesis concept remains dominant in current understanding of the pathogenesis of emphysema. However, as pointed out in this review, this may represent too narrow a focus. The role of oxidants, malnutrition, lung repair, and infections all merit consideration. Other potentially important factors not considered here include genetic factors and behavioral patterns. These may be important in explaining why only a small proportion of the smoking population develops symptomatic emphysema. A better understanding of the pathogenesis of emphysema is needed so that methods of interrupting the process can be designed and tested. Many tracts must be pursued using a multiplicity of approaches and techniques in order to define the basis for the disease.