Activation of the renin-angiotensin-aldosterone and adrenergic nervous systems plays a major role in the progression of heart failure, and inhibitors and antagonists of these neurohormonal systems improve outcomes. b-Blockers, angiotensin-converting enzyme inhibitors, and aldosterone antagonists have been shown to improve parameters such as ventricular remodeling, ejection fraction, and renal function and to reduce rates of morbidity and mortality. This article reviews 3 recent clinical trials that have added to our knowledge of the use of these agents. Two of the studies-EPHESUS and COMET-demonstrated significant reduction in all-cause mortality, whereas the third-CHARM-showed a marginal reduction. These trials established that it is feasible to design and execute heart failure studies of sufficient scale to assess improvement in rates of mortality and morbidity.