The Multi-Ethnic Study of Atherosclerosis (MESA) is the first large-scale multi-ethnic population study in the U.S. to use advanced cardiovascular magnetic resonance (CMR) imaging. MESA participants were free of cardiovascular disease at baseline between 2000 and 2002, and were followed up between 2009 and 2011 with repeated CMR examinations as part of MESA. CMR allows the clinician to visualize and accurately quantify volume and dimensions of all four cardiac chambers; measure systolic and diastolic ventricular function; assess myocardial fibrosis; assess vessel lumen size, vessel wall morphology, and vessel stiffness. CMR has a number of advantages over other imaging modalities such as echocardiography, computed tomography, and invasive angiography, and has been proposed as a diagnostic strategy for high-risk populations. MESA has been extensively evaluating CMR imaging biomarkers, as markers of subclinical disease, in the last 15 years for low-risk populations. On a more practical level, some of the imaging biomarkers developed and studied are translatable to at-risk populations. In this review, we discuss the progression of subclinical cardiovascular disease and the mechanisms responsible for the transition to symptomatic clinical outcomes based on our findings from MESA.