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Gene therapy is an exciting frontier in medicine today. Radiologists will be involved in tracking the effects of these new therapies through imaging. Vascular and interventional radiology techniques also are ideally suited for minimally invasive, readily monitored gene delivery. Gene therapy is accomplished through gene augmentation or gene blocking. The latter is accomplished through antisense oligonucleotides or transcription factor decoys. Vectors are agents that facilitate gene delivery and expression and can be viral or nonviral. The vascular wall is an ideal target for gene therapy because of its central role in many biologic processes and its ready accessibility. Recombinant genes can be delivered ex vivo and in vivo, with the latter approaches involving open surgical, percutaneous injection, and endovascular catheter-based methods. Perforated, hydrogel-coated, and double balloon catheters have been used with varying success. Optimal catheter systems for gene transfer will enable delivery of the vector to the precise anatomic location with transfection limited to the cells of interest and will minimize shedding of the vector to distal sites, systemic effects of the therapeutic agent, and morbidity from the delivery method. Radiologists must become familiar with the basic rationale, strategies, and mechanisms of gene therapy and involved in its clinical trials to ensure an active role in this field.