The clinical consequences of stent thrombosis are frequently catastrophic. This article reviews the factors previously implicated in the occurrence of stent thrombosis and analyzes recent reports of thrombosis involving a new sirolimus-eluting stent (Cypher). Factors associated with stent thrombosis include intrinsic stent thrombogenicity and patient-, target lesion-, and procedure-related issues. Stent design may influence the degree of platelet activation after coronary stent deployment. In drug-eluting stents, the mechanical properties of the bare metal stent platform might be altered by the polymer coating, and the propensity for thrombosis might be influenced by both the polymer coating and the medication with which it is impregnated. Cumulative data for the Cypher stent do not suggest a propensity for thrombosis, but several caveats should be observed to enhance the safety of the device.