Heart failure is a progressive condition with a 5-year survival of less than 50%. This poor prognosis, which can be reproduced by overloading the hearts of experimental animals, may reflect molecular abnormalities caused when overload stimulates adult cardiac myocytes to undergo hypertrophy. Because these terminally differentiated cells have little or no capacity to divide, hypertrophy represents an unnatural growth response; however, the mechanism by which overload shortens survival remains speculative. Modification of this unnatural growth response by converting enzyme inhibitors and nitrates, which have growth inhibitory as well as vasodilator effects, may contribute to the ability of these drugs to improve prognosis in patients with heart failure.