beta-adrenergic receptors (betaAR) belong to the large family of G protein-coupled receptors that form the interface between the sympathetic nervous and cardiovascular systems. G protein-coupled receptors undergo adaptation to repeated or prolonged agonist stimulation, which is termed desensitization. Significant betaAR desensitization occurs with the development of cardiac hypertrophy and heart failure, and uncoupling of betaARs and defects in this pathway might be primary elements underlying the transition from compensated to uncompensated cardiac failure. Decreasing the level of myocardial betaARK1 in established heart failure is a novel approach to improving impaired betaAR receptor function, and potentially alter the pathogenesis of this disease.