The reasons to measure atherosclerosis include 1) risk stratification and prediction; 2) evaluation of patient response to interventions; and 3) identification of novel genetic, cellular and molecular determinants of risk. Atherosclerosis can be quantified non-invasively using the increasingly reliable and precise modalities described in this issue, which include ultrasound and magnetic resonance imaging. While each modality assesses “atherosclerosis”, the particular morphological entities captured may reflect different aspects of atherogenesis with different biological determinants. For instance, among carotid ultrasound determinations, intima-media thickness (IMT) may reflect medial hypertrophy from hypertension, while plaque volume and stenosis and calcium deposition may additionally reflect foam cell proliferation, scarring and / or thrombosis. Clarifying the biological and clinical correlates of images may guide the choice of modality for specific applications. In addition, these tools are presently used to assess structures at a single time point. However, using them to follow temporal changes may further enhance their value. In this regard, certain modalities, such as ultrasound assessment of carotid plaque area or volume, may be more sensitive than others, such as assessment of IMT, for detecting temporal changes in atherosclerosis. Combining modalities - and adding new biomarkers of disease - may be necessary to grasp the full complex vascular phenotypic picture - “phenomics” - of both individual subjects and groups of patients. In evaluating new determinants and novel therapies, it will be important to consider the biology and clinical correlates of a specific measured atherosclerosis phenotype in order to select the most appropriate modality.