Advances in computed tomographic (CT) imaging of the lung in the past decade, particularly with increased speed, resolution, gating capability, and rapidly expanding volumetric image acquisition, along with advances in image processing, have expanded the repertoire of imaging methods beyond anatomic visualization into the noninvasive study of regional lung physiological function. Recognizing that significant local disease or dysfunction can exist before global measures begin to deteriorate, the motivation for the development and application of these regional techniques is to further our understanding of the basic pathophysiological characteristics of evolving lung disease and, ultimately, develop sensitive measures for its early detection. This review emphasizes the key elements of ventilation and lung mechanics relevant for regional approaches and CT measurement principles available for their study. Examples of established and evolving methods for imaging regional ventilation and mechanics, including the xenon CT ventilation method; the relationship between changing regional CT density and air volume change; and registration-based methods for examining regional lung expansion and strain, are presented.