It is now more than two decades since Nico Pijls and Bard DeBruyne introduced fractional flow reserve (FFR) as a way to assess stenosis severity in the catheterization laboratory and since Paul Yock invented grayscale intravascular ultrasound (IVUS) that then spawned many second-generation intravascular imaging techniques such as (1) Virtual histology-IVUS (VH-IVUS) that uses both amplitude and radiofrequency ultrasound information to classify plaque as necrotic core,fibrofatty,fibrotic,or calcific;(2) Optical coherence tomography (OCT) that is the light analogue of IVUS with a 10-fold increase in resolution and better tissue characterization,but at the expense of decreased penetration;(3) Near infrared spectroscopy (NIRS) that detects lipid within the vessel wall within 0.45 mm of the neointimal surface and that has been recently combined with grayscale IVUS in a single catheter.