Improved understanding of the pathophysiology of chronic lung disease at a molecular and cellular level has led to the concept of targeted pharmacotherapy for the modification of disease progression. The limitations of conventional physiological measures of disease have prompted the development of alternative methods for determining outcome in therapeutic trials. Technological improvements in computed tomography, coupled with the development of software for the automated calculation of densitometric parameters have resulted in more specific and sensitive measures of disease than traditional methods. Such techniques have been applied principally to the assessment of changes in lung parenchyma in patients with chronic obstructive pulmonary disease and, in particular, in patients with α1-antitrypsin deficiency where they have been used as an outcome measure in a therapeutic trial of α1-antitrypsin augmentation. Measurement of airway dimensions has proved more problematic and most studies have, until recently, been limited to anthropomorphic phantoms orex-vivospecimens.This paper reviews the development of quantitative computed tomography and explores its potential role as an outcome measure in trials of disease-modifying therapy.