The goal of quantitative analysis of computed tomography (CT) scans is to understand the anatomic structure that is responsible for the physiological function of the lung. The gold standard for structural analysis requires the examination of tissue, which is not practical in most studies. Quantitative CT allows valuable information on lung structure to be obtained without removal of tissue from the body, thereby aiding longitudinal studies on chronic lung diseases. This review briefly discusses CT analysis of the lung and some of the sources of variation that can cause differences in the CT metrics used for analysis of lung disease. Although there are many sources of variation, this review will show that, if the study is properly designed to take into account these variations and if the CT scanner is properly calibrated, valuable information can be obtained from CT scans that should allow us to study the pathogenesis of lung disease and the effect of treatment.