Advances in vascular biology and the study of molecular pathophysiology have enabled the design and initial testing of therapeutic principles for cardiovascular intervention at the level of gene expression. This approach can offer an avenue to greatly impact the onset and progression of vascular disease at its roots. Early translations of basic research into human clinical protocols might provide novel alternatives for patients without traditional therapeutic options and might provide means of improving and prolonging the success of standard therapies. As the understanding of the genetic basis of vascular disease continues to grow and the tools for in vivo genetic manipulation continue to improve, vascular gene therapies might someday become a part of routine patient care.