The transformation of cardiac care over the past half century has been breathtaking to witness. In large part, this transformation is due to the advent of new drugs and devices, improved health care systems, and behavioral modifications such as smoking cessation. Four cardiac medicines developed before 1960 that survived the turn of the millennium are aspirin, digoxin, warfarin, and spironolactone. New competitors threaten the continued longevity of aspirin, the survival of digoxin depends on evidence of its ability to improve exercise tolerance and quality of life in patients with heart failure, and new pretenders for warfarin are here. Remarkably, after over 50 years, the aldosterone antagonism achieved by spironolactone (and more recently eplerenone) has earned an enduring role in the treatment of heart failure.