Gene therapy techniques are under development for many areas of medicine, including cardiovascular disease. Identifying appropriate gene targets will require more detailed knowledge of the molecular pathophysiology of these disorders, and choosing appropriate vectors and delivery systems will contribute significantly to the challenge of developing this approach for clinical use. The concepts of toxicology and therapeutic drug monitoring will need to be broadened to account for the unique chemical, biological, and genetic characteristics of gene therapeutic agents. This review will provide an overview of strategy development, currently available vectors, and examples of their application to cardiovascular gene transfer. Considerations of the potential toxicities associated with particular vectors and delivery systems, as well as the types of genetic modifications possible, will provide some guidelines regarding appropriate monitoring of their clinical application.