Encouraging preliminary data suggest that gene therapy may soon be an option for the treatment of patients with advanced coronary artery disease that is not amenable to conventional treatment. A critical consideration in developing cardiovascular gene transfer as a therapy is the ability to deliver the vector, viral or plasmid, to the desired tissue in a safe fashion. Attempts at developing non-viral direct DNA therapy delivered through the intravenous route are currently underway and with the use of advanced technology the possibility of making gene therapy a simple outpatient procedure does not seem out of the realm of possibility. Several clinical trials are currently underway that should help characterize the risk–benefit profile of various products, the optimal dose that should be administered, and the patient population likely to derive greatest benefit.