Gene transfer represents a method for treatment of several cardiovascular disorders, including endothelial dysfunction and hypertension. For effective and safe gene therapy in vascular disease, a suitable therapeutic gene needs to be identified and delivered to the vasculature by appropriate delivery devices. In this chapter, we review the different vectors used, both viral and nonviral, suitable genes identified, and associated delivery devices. Several genes have been identified with a view to improve endothelial dysfunction, and we have elaborated the advantages and disadvantages of these approaches. Strategies to treat hypertension, both systemic and pulmonary, have also been described. The optimal vector has not yet been discovered although a wide variety of choices is available, each with properties that may render it suitable for specific applications. The individual characteristics of these vectors are described in relation to the proposed therapeutic paradigm. Although there are several unanswered questions in this arena, the future application of gene transfer technology to diseases of the vasculature holds significant promise.