Cardiac gene delivery has become an important issue following the emergence of gene therapy for the possible treatment of heart failure. Despite many advances in the management of heart failure (HF), treatment options for many patients with advanced HF remain limited. At a cellular and molecular level, many of the fundamental alterations that contribute to the pathogenesis of HF are becoming better understood and this has resulted in the discovery of new therapeutic targets in animal models of HF, in particular in the area of gene therapy. Numerous small animal and preclinical studies have examined the efficacy of delivering genes targeting various signaling pathways that are affected as the heart fails. However, the translation of this work into the clinic has been difficult due to the requirement for large scale targeted delivery of the gene. This methods chapter describes a percutaneous method of recirculation that we have employed to successfully deliver potential therapeutic agents, including genes, to the heart.