The acute technical success of percutaneous transluminal angioplasty (PTA) has been improved with the use of intravascular stents. However, stent placement has led to the development of an increased myointimal hyperplastic response leading to late reduction in vessel lumen. Restenosis (> or =50% reduction in reference lumen diameter) rates for coronary angioplasty and stenting are reported between 20% and 50% at 1 year. Several studies are currently evaluating novel delivery of antiproliferative agents to prevent neointimal hyperplasia. The authors review the mechanism of neointimal hyperplasia as it relates to stent placement and discuss recent and ongoing trials evaluating intravascular brachytherapy and drug-eluting stent technology in the inhibition of restenotic lesions.