Drug-eluting stents (DES) have revolutionized interventional cardiology. The profound ability of DES to suppress neointimal hyperplasia results in a reduced need for revascularization and improved clinical outcomes. DES, however, are not immune to in-stent restenosis. This problem particularly affects DES implanted for "off-label" indications and in challenging clinical and anatomic scenarios. In addition, as compared to bare-metal stents, DES do not reduce the incidence of stent thrombosis. Therefore, optimization of DES deployment is becoming increasingly important and, in this regard, intravascular ultrasound (IVUS) provides unique insights. IVUS assessment of neointimal growth has been of major value to understand the mechanisms of action of DES and also to compare different DES. Notably, IVUS enables optimization of DES implantation. DES underexpansion, edge-restenosis, residual dissections, plaque prolapse, stent fracture, incomplete stent apposition and DES-related aneurysms, are readily assessed by IVUS. The use of IVUS to study and manage DES failures (namely in-stent restenosis and DES thrombosis) is of major value. In conclusion, IVUS provides unique insights during DES implantation, allows DES optimization and should always be used during the management of DES failures: in-stent restenosis and DES thrombosis.