Ongoing advances in peripheral endovascular technology have been met with disappointing results because of restenosis within the treated vessel. In particular, stent balloon angioplasty of peripheral vessels has yet to achieve patency rates that approximate conventional treatment in the long term. Recent advances in stent, balloon, and wire construction include the incorporation of radioactive substances in an attempt to ameliorate the inflammatory response provoked by typical endovascular manipulation, a technique termed vascular brachytherapy. gamma- and beta-isotopes and external beam radiation target the very cell population whose activity results in the development of neointimal hyperplasia. Although most clinical research examining the efficacy of vascular brachytherapy has emerged from the coronary artery literature, the use of vascular brachytherapy also has been examined in the peripheral arterial tree and has shown promising results. Current data indicate that vascular brachytherapy is a safe and accessible adjunctive endovascular maneuver that may improve the short-term patency rate of peripheral endovascular applications. The effects on long-term patency rates remain indeterminate compared to conventional therapy.