The results of three clinical studies (OVERTURE, ENABLE and RENEWAL), in patients with cardiac failure, are analyzed from a pharmacological point of view. In the first one of these, the action of an Angiotensin Converting Enzyme inhibitor, that at the same time inhibits the neutral endopeptidase, is studied. In the second, a blockade for endothelin cellular receptors is studied and, in the third, a synthetic acceptor of the alpha-Tumoral Necrosis Factor is taken into account. In the OVERTURE study, the benefit action of the inhibition of the Angiotensin Converting Enzyme in patients suffering from cardiac failure is confirmed, without a major effect from the neutral endopeptidase derived from its simultaneous inhibition. The other two studies were suspended because of the major side effects. The drugs used in OVERTURE, ENABLE and RENEWAL studies are relevant efforts of molecular design that, without any question, will project into the future of the therapeutic approach of cardiac failure. It is convenient to point out that in the task of designing clinical studies considering cellular signaling systems, there are other venues warranting their use in pathological or natural functions.