Emphysema is a major constituent of lung pathology in chronic obstructive pulmonary disease, and emphysema is characterized by loss of lung tissue. Computed tomography (CT) generates detailed information on tissue densities, and lung density by CT has the potential of being both more sensitive and specific for monitoring emphysema in clinical trials than more traditional outcome measures such as pulmonary function tests. However, CT measurements of lung density are subject to many sources of noise, such as variations in the scanning procedure (technical noise) and variations in patient performance (biological noise). A multi-detector array scanner and a low-dose volumetric scanning protocol are recommendable, and images should be reconstructed using a soft filter. In longitudinal studies the percentile density (PD) is the most reproducible densitometric parameter, and confounding due to variations in inspiratory level can be adjusted for by a physiologic model that assumes that the lung behaves like a sponge. Work remains to be done to standardize and validate CT lung density, before it can become established as the primary outcome measure in clinical trials of new treatments for chronic obstructive pulmonary disease.