The quest for an anti-restenotic drug continues to be a major challenge in the field of cardiovascular pharmacology because most therapies with proven efficacy in experimental neointima models have failed to limit restenosis. Some drug classes, including glycoprotein IIb/IIIa antagonists, nitric oxide donors and the antioxidant probucol, have recently demonstrated potential benefits in clinical trials. Progress in the development of local delivery systems for administration of drugs, antisense oligonucleotides or genes, in combination with an improved understanding of the pathogenesis of restenosis holds promise for ultimate pharmacotherapy of this condition.