Motivated by the promise to transform preclinical research and clinical care, cardiovascular molecular imaging has made advances toward targeting coronary atherosclerosis and heart failure. Here, we discuss recent progress in the field, highlight how molecular imaging may facilitate preventive patient care, and review specific challenges associated with coronary and heart failure imaging. Practical considerations stress the potential of fluorescence imaging for basic research and discuss hybrid protocols such as FMT-CT and PET-MRI.