In recent years there has been a rapid expansion in our understanding of the molecular biology that underpins human physiology. In the heart, elegant molecular pathways have been elucidated, and derangements in these pathways have been identified as factors in cardiac disease. However, as our understanding has grown, we have recognized that there exist only relatively crude tools to effect changes in molecular pathophysiology. The ultimate promise of gene therapy is to correct the molecular derangements that cause illness. To bring this promise to fruition in the clinical arena, many problems need to be solved, and chief among these remains reliable and robust delivery of genes to the target organ. To this end, viral vectors have been utilized with success more frequently than any other method of gene delivery. The use of these vectors in the heart has already offered promising novel benefit for human ischemic heart disease, and studies in animal models have given glimpses of hope that gene therapy may provide future therapeutic benefit in heart failure by improving cardiac function.