Technology of drug-eluting stent (DES) implantation is relatively young. DES have remarkably reduced the incidence of stent-restenosis (SRS) and the need for target vessel revascularization (TVR). Yet it has added a small but significant risk of late and very late stent thrombosis (ST). The incidence of ST varies between 0.3-2.8% with a mean of 1.3%. ST occurs both with bare-metal stents (BMS) and drug-eluting stents (DES) but the time course differs with an excess of ST in the first six months of implantation with BMS while the number of ST is more with DES after 6 months of implantation. Despite this difference, there are no overall differences between BMS and DES regarding the end points of death or myocardial infarction (MI) on long term (3-5 years) follow-up. Endothelial dysfunction and incomplete neointimal coverage of stent strut remain the basic underlying mechanisms responsible for ST in DES. Stent thrombosis, though infrequent, is a dreadful condition. Over 30% may die suddenly. 60% develop massive MI with cardiogenic shock, poor LVEF and serious arrhythmias. The beneficial effects of primary percutaneous intervention (PCI) for ST are not spectacular, and TIMI flow grade III, is achieved in less than 80% cases, while distal embolization and residual dissection of coronary artery are frequently encountered. Proper selection and optimization of stent with prolonged dual antiplatelet therapy may prevent the undesirable stent thrombosis after DES implantation.