Quantitative imaging has been proposed as the next frontier in radiology as part of an effort to improve patient care through precision medicine. In 2007, the Radiological Society of North America launched the Quantitative Imaging Biomarkers Alliance (QIBA), an initiative aimed at improving the value and practicality of quantitative imaging biomarkers by reducing variability across devices, sites, patients, and time. Chest CT occupies a strategic position in this initiative because it is one of the most frequently used imaging modalities, anatomically encompassing the leading causes of mortality worldwide. To date, QIBA has worked on profiles focused on the accurate, reproducible, and meaningful use of volumetric measurements of lung lesions in chest CT. However, other quantitative methods are on the verge of translation from research grounds into clinical practice, including (a) assessment of parenchymal and airway changes in patients with chronic obstructive pulmonary disease, (b) analysis of perfusion with dual-energy CT biomarkers, and (c) opportunistic screening for coronary atherosclerosis and low bone mass by using chest CT examinations performed for other indications. The rationale for and the key facts related to the application of these quantitative imaging biomarkers in cardiothoracic chest CT are presented. ©RSNA, 2019 See discussion on this article by Buckler (pp 977-980).