Acute coronary syndrome (ACS) arising from plaque rupture is the leading cause of mortality worldwide. Near-infrared spectroscopy (NIRS) combined with intravascular ultrasound (NIRS-IVUS) is a novel catheter-based intravascular imaging modality that provides a chemogram of the coronary artery wall, which enables the detection of lipid core and specific quantification of lipid accumulation measured as the lipid-core burden index (LCBI) in patients undergoing coronary angiography. Recent studies have shown that NIRS-IVUS can identify vulnerable plaques and vulnerable patients associated with increased risk of adverse cardiovascular events, whereas an increased coronary plaque LCBI may predict a higher risk of future cardiovascular events and periprocedural events. NIRS is a promising tool for the detection of vulnerable plaques in CAD patients, PCI-guidance procedures, and assessment of lipid-lowering therapies. Previous trials have evaluated the impact of statin therapy on coronary NIRS defined lipid cores, whereas NIRS could further be used as a surrogate end point of future ACS in phase II clinical trials evaluating novel anti-atheromatous drug therapies. Multiple ongoing studies address the different potential clinical applications of NIRS-IVUS imaging as a valuable tool for coronary plaque characterization and predictor of future coronary events in CAD patients.