Disorders of the vascular system are the leading cause of death and disability in the Western world. Mechanical interventions, such as angioplasty and bypass grafting, constitute the mainstay of treatment for end-stage occlusive lesions. Although initially successful in the majority of cases, the vascular response to injury and subsequent restenosis limits their long-term efficacy. Current work in the field of gene therapy has focused on the development of strategies to prevent these complications by the use of recombinant DNA technology. This review focuses on the latest advances in gene therapy for vascular disease, including the development of new vectors for vascular gene delivery, novel treatments for angioplasty-induced restenosis and vein graft intimal hyperplasia, and therapeutic angiogenesis.