Hope has been expressed that gene and cell therapies will one day reduce the morbidity and mortality associated with cardiovascular diseases. Work in these fields has shown that the road from bench to bedside is filled with obstacles. Still, the possibility for treatment or even cure of cardiac disease is real. Continuing work will improve understanding of the underlying physiology and vector biology. The current review focuses on the potential use of gene therapy to affect cellular communication. Included is a review of communication effects on a transcellular level with angiogenesis, AV nodal conduction and sinus nodal automaticity, and effects on an intracellular level with cardiac myocyte repolarization. Challenges facing the field of gene therapy are also reviewed. If these problems can be solved, gene therapy will become a viable alternative for clinical use.