Myocardial gene therapy was born at the beginning of the 90's from the marriage of well-defined pathophysiological mechanisms with recombinant adenovirus technology. Together with the development of relatively simple vector delivery procedures during the last few years, this made it possible to consider the possibility of treating diseases such as ischemic cardiomyopathies by the delivery of angiogenic factors and to bring the first proof, in rats, that myocardial gene therapy for experimental heart failure can improve cardiac performance and prolong life duration of the animals. It is now conceivable that such an approach will be applied to human heart failure within the next years. In contrast, regarding familial cardiomyopathies and channelopathies, because of the specificity of each disease type and complexity of the pathophysiology of each mutation, it is likely that much more time will be necessary. However, a number of barriers still exist before myocardial gene therapy can spread to the field of routine clinical cardiology, including finding a safe vector allowing good transduction efficiency rates to cardiac myocytes when delivered through coronary arteries. In contrast, it is conceivable that in the open chest setting, myocardial gene therapy will rapidly be used by surgeons, by itself or in association with the injection of "wild" cells or cells transfected with various types of genes. It can now be assumed that such biotherapies will soon offer patients suffering from myocardial diseases (and especially heart failure) the perspective of major therapeutic progresses.