Vascular gene transfer offers a promising alternative for the treatment of cardiovascular diseases. Blood vessels are among the easiest targets for gene therapy and in most conditions only a temporary expression of the transfected gene will be required to achieve a beneficial biological effect. Adenoviruses lead to most efficient transgene expression in arterial wall. Depending on the treatment requirements, gene transfer to the artery wall can be accomplished both from lumen and from adventitia. Promising therapeutic effects have been obtained in animal models of restenosis with the transfer of vascular endothelial growth factor (VEGF), nitric oxide synthase, thymidine kinase, retinoblastoma, growth arrest homeobox gene and antisense oligonucleotides against transcription factors or cell cycle regulatory proteins. First experiences of VEGF gene transfer to human peripheral arteries have also been reported. However, further studies regarding gene transfer techniques, vectors and safety of the procedures are needed before a full therapeutic potential of gene therapy in vascular diseases can be evaluated.