Virtually all medications used to treat cardiac problems act through a pharmacological mechanism that immediately improves electrical or mechanical function or inhibits the manifestation of a pathological process. The idea that medical therapy could exert a favourable myocardial effect by fundamentally improving the biological function of cardiac myocytes is novel, and is based on the observation that in heart failure the acute pharmacological effects of beta-blocking agents on left ventricular function are completely different from their long-term effects. beta-blocking agents improve intrinsic systolic function long-term, despite depressing function initially through the pharmacological effect of withdrawing adrenergic drive, indicating that the beneficial effect of this form of therapy is due to improved myocyte biology. Implicit in this observation is that improvement in the fundamental biology of failing cardiac myocytes should favourably affect the natural history of heart failure.