In in-stent restenosis, drug-eluting stents are superior compared with bare metal stents. However, there are concerns about safety because of the reports of increased risk of late and very late stent thrombosis. Stent thrombosis remains a major pitfall in contemporary percutaneous coronary intervention, leading to high rates of death and nonfatal myocardial infarction. A new standardized definition of stent thrombosis was established to provide consistency in the reporting of this complication and to enable accurate and reliable data to be described for both types of stents, bare metal and drug-eluting. This new consensual definition reflects a large amount of new data reported in the literature. New generations of drug-eluting stents with novel polymers, antiproliferative drugs, and improved platforms are now approved and available for use. In this article, the authors provide a critical appraisal of the safety of different drug-eluting stents based on the published clinical data focusing on late and very late stent thrombosis.