A major impediment in the development of novel drugs for chronic obstructive pulmonary disease (COPD) has been the scarcity of a well-validated, robust, and easily obtainable intermediate end point such as serum biomarkers. To date the best serum biomarkers in COPD have been non-speci"c pro-in"ammatory molecules synthesized largely by extra-pulmonary organs. In COPD, an ideal biomarker would be one that (1) was produced mostly in the lungs (and was reliably measurable in the peripheral circulation using commercially available kits), (2) changed with the clinical status of patients or with relevant exposures; and (3) had inherent functional attributes that suggested a possible causal role in the pathogenesis of the disease. In this paper, we review one promising systemic biomarker that ful"lls some of these criteria, surfactant protein D (SPD).