Advances in our understanding of the molecular basis of coronary heart disease provide an opportunity to treat this disease at the genetic level by gene therapy approaches. Adeno-associated viral (AAV) vectors are perhaps one of the most promising gene delivery systems under development. AAV vectors deliver genes to various organs and provide for long-term gene expression. The ideal vehicle for cardiac gene therapy would provide therapeutic gene expression in the heart and avoid off-target gene expression in irrelevant tissues. This seminar will review recentdevelopments in using of AAV vectors for accomplishing cardiac-specific gene expression after systemic administration in mice, and describe the effects of cardiac specific over-expression of inducible nitric oxide synthase on cardiac structure and function.