The implementation of coronary brachytherapy and especially the application of drug-eluting stents for the prevention of in-stent restenosis are of vital importance in the field of interventional cardiology. Despite undeniable benefits of these new methods a potential increased risk for the occurrence of stent thrombosis as a result of the mode of action of these new methods has to be taken into consideration. The prevention of stent thrombosis following coronary brachytherapy and implantation of drug-eluting stents is therefore of particular importance to assure the success of these forward-looking technologies. This article provides an overview of current data regarding the incidence of stent thrombosis following brachytherapy and implantation of drug-eluting stents and it's implication for clinical practice.