Stent thrombosis has become a major concern for interventional cardiology. Although infrequent, it is associated with significant morbidity and mortality. Recent attention has focused on the frequency of this complication with drug-eluting stents compared with bare-metal stents in regard to the timing (early, late, or very late) of the event, underlying mechanisms involved, and preventive strategies. Although dual antiplatelet therapy (aspirin plus thienopyridine) is crucial in mitigating the problem, there are significant issues with this management strategy, including the duration of dual antiplatelet treatment, patient compliance, variability in individual response to therapy, bleeding risk, and management of subsequent noncardiac surgical procedures. Newer strategies being evaluated to enhance the safety of drug-eluting stents include different alloys and stent designs, revisions in the polymer or drug utilized, and, ultimately, bioabsorbable platforms.