Drug-eluting stents (DES) promise to change the landscape of interventional cardiology, overcoming restenosis that is the major limitation of percutaneous coronary interventions. Intravascular ultrasound (IVUS) examination has been at the centre of our efforts to understand the mechanisms and define different treatment strategies during coronary interventions. IVUS interrogation and 3-dimensional IVUS measurements have been used to better define the mechanisms of benefit and potential drawbacks of DES. The findings of these studies are summarized in this article and the potential importance of IVUS in the era of DES is discussed. Evidence of neointimal hyperplasia (IH) suppression and assessment of any edge effect or vessel remodeling after implantation of DES has been evaluated by IVUS. The overall clinical importance of IVUS in the new era will depend on the amount and the clinical significance of any unsolved questions we will face and on its ability to provide answers to the evolving questions.