Vascular brachytherapy using beta and gamma emitters has revolutionized treatment of in-stent restenosis. We are witnessing a near-abolition of the restenosis problem for simple lesions, but the future of vascular brachytherapy depends on our success in improving efficacy and reducing complications such as late thrombosis and edge effects. Optimizing dosimetry, applying adequate radiation margins, and prolonging antiplatelet therapy should equalize brachytherapy results with those of drug-eluting stents. In this overview we examine issues related to progress and optimization of outcomes derived from the use of vascular brachytherapy. We also examine its potential to expand to other applications beyond in-stent restenosis, such as the treatment of de novo lesions and peripheral vascular disease.