Drug-eluting stents (DESs) held the promise of mitigating, if not abolishing, in-stent restenosis. This led to early adoption and high penetration of DES use in percutaneous coronary intervention (PCI). Outcomes have not demonstrated an improvement in the hard end points of death and myocardial infarction with these devices, but repeat procedures for in-stent restenosis have decreased. The problem of stent thrombosis, a major obstacle that arose early in coronary stent development, has raised new contemporary concerns about the safety of DESs. The risk for stent thrombosis after bare metal stent placement appears to diminish with time, while very late stent thrombosis (>1 year after index PCI) occurs in small but measurable numbers after DES placement at a rate that continues to increase. Late-acquired incomplete stent apposition and abnormal endothelial function have also been reported. Restenosis, although significantly lessened, does occur after DES PCI. This report reviews DES safety issues that have been described.