Major advances in molecular biology over the past decade have increased our understanding of how genes are expressed and regulated in mammalian cells in vivo. This knowledge has been translated to investigations of the molecular and cellular biology of the cardiovascular system. Gene transfer, the introduction of a recombinant gene into host somatic cells, has become a useful tool for studying gene structure and function. It can be used to identify regulatory sequences that control gene expression. Transfer of a gene into a new cellular environment provides a means to determine gene function. These methods also allow investigators to introduce new genes into intact animals, permitting the development of animal models of human disease and investigations of gene function in vivo. The field of gene transfer and vascular disease is emerging as a new approach for studying the pathophysiology of vascular disease and for developing potential new genetic treatments for these disorders. In this review, we discuss the methods for gene transfer, how these methods can be employed to investigate the pathophysiology of cardiovascular diseases, and the potential for the development of molecular genetic treatments for human vascular diseases. The focus will be on cardiovascular diseases, although the principles may be applied to other disorders. In summary, gene transfer represents a new approach to applying molecular biology to the study and treatment of human disease.