Cardiovascular disease is a major cause of morbidity and mortality in the contemporary society. Cardiac gene therapy has already been investigated in clinical studies profoundly. Adenovirus vector could transfer the gene efficiently, but low organ specificity and immuno- genie properties limited its application, With adenovims vector improved in the last few years, the third adenovims vector is probably the most potential vector systems for cardiovascular disease. This review will give a broad overview of the molecular basis of the adenovims vectors, their advantages, the development of increasingly efficient gene transfer approach, and experimental and clinical studies targeting the heart, application barriers and modified strategies.