Molecular therapy is emerging as a potential strategy for the treatment of cardiovascular disease such as restenosis after angioplasty, vascular bypass graft occlusion and transplant coronary vasculopathy, for which no known effective therapy exists. One strategy for combating disease has been to target the transcriptional and translational processes. Three approaches have been used to accomplish this. One approach is the use of antisense oligodeoxynucleotides (ODN) that are complimentary to the messenger RNA (mRNA) of interest. The second approach is the use of ribozymes, a unique class of RNA molecules that not only store information but also possess catalytic activity. Ribozymes are known to catalytically cleave specific target RNA species, leading to their degradation, whereas antisense molecules inhibit translation by binding to mRNA sequences on a stoichiometric basis. Thus, theoretically, ribozymes are more effective in inhibiting target-gene expression. A third approach is the transfection of cis-element double-stranded decoy ODN. Transfection of decoy ODN will result in attenuation of authentic cis-trans interaction, leading to the removal of trans-factors from the endogenous cis-elements, with subsequent modulation of gene expression. This novel decoy ODN strategy not only promises therapeutic potential but also represents a powerful tool for the study of endogenous gene regulationin vivoas well asin vitro. In particular, early work relating to graft restenosis appears promising. The application of DNA-based therapies to regulate the transcription of disease-related genesin vivohas important therapeutic potential.