Chest CT scans are one of the most common medical imaging procedures. The automatic extraction and quantification of imaging features may help in diagnosis, prognosis of, or treatment decision in cardiovascular, pulmonary, and metabolic diseases. However, an adequate sample size as a statistical necessity for radiomics studies is often difficult to achieve in prospective trials. By exploiting imaging data from clinical routine, a much larger amount of data could be used than in clinical trials. Still, there is only little literature on the implementation of radiomics in clinical routine chest CT scans. Reasons are heterogeneous CT scanning protocols and the resulting technical variability (eg, different slice thicknesses, reconstruction kernels or timings after contrast material administration) in routine CT imaging data. This review summarizes the recent state of the art of studies aiming to develop quantifiable imaging biomarkers at chest CT, such as for osteoporosis, chronic obstructive pulmonary disease, interstitial lung disease, and coronary artery disease. This review explains solutions to overcome heterogeneity in routine data such as the use of imaging repositories, the standardization of radiomic features, algorithmic approaches to improve feature stability, test-retest studies, and the evolution of deep learning for modeling radiomics features.