Purpose of reviewTo provide an update on clinical trials of gene therapy for atherosclerotic cardiovascular disease published since 1 August 2001 and summarize the general advantages and potential problems of gene transfer in these disorders.Recent findingsThere are two major areas in which gene therapy has entered clinical trials. The first is angiogenesis for coronary and peripheral arterial disease. Two relatively small placebo-controlled trials for coronary disease were reported, one using intramyocardial plasmidVEGF-2gene, the other using intracoronary adenoviralFGF-4gene. TheVEGF-2study in no-option patients showed reduced angina, and significant improvement in perfusion and function, whereas theFGF-4study in less severely affected patients showed promising results in some subsets. In peripheral artery disease two phase 1 studies of adenoviralNV1FGFandVEGFshowed some objective improvement in pain, ulcer size and ankle : brachial index in one study and endothelial function in the other. Both adenoviral and plasmidVEGFgene transfer at angioplasty increased vascularity in a phase 2 double-blind study. The other major area is the prevention of graft disease and restenosis using antisense oligodeoxynucleotides. E2F decoy led to a significant reduction in venous graft complications after ex-vivo transfection at the time of coronary bypass surgery, whereas the c-Myc oligodeoxynucleotide was ineffective in preventing in-stent coronary restenosis.SummaryThere are more reviews of gene therapy for atherosclerosis in the literature than publications with original data or trials, but in the past year the imbalance is being redressed, with some promising results from controlled studies.