Progression of vulnerable coronary atherosclerotic plaques underlies most episodes of acute myocardial infarction and sudden cardiac death. Recent advances in biological/molecular imaging technology are now enabling the accurate identification of high-risk plaques and coronary stents in living subjects. Due to their smaller caliber and susceptibility to cardiorespiratory motion, noninvasive molecular imaging of human coronary arteries remains challenging. Therefore, intravascular high-resolution molecular imaging approaches appear necessary to resolve molecular features of human coronary arteries and stents. Here we present recent progress in intravascular near-infrared fluorescence (NIRF) molecular imaging, including the evolution from stand-alone NIRF systems to those integrated with structural imaging methods including optical coherence tomography and intravascular ultrasound. Preclinical demonstrations of imaging inflammation, fibrin, and endothelial impairment are highlighted. We then close with a discussion of translation of NIRF imaging to the cardiac catheterization laboratory and showcase first-in-human intracoronary imaging results of NIR autofluorescence in CAD.