A number of neurohormones are activated in chronic heart failure (CHF), which have either vasoconstrictor or vasodilator effects. Excessive neurohormonal production has deleterious effects in the long term, leading to progression of CHF through a variety of mechanisms including necrotic and apoptotic myocyte death, myocardial fibrosis, and continuous left ventricular remodeling. Neurohormonal activation begins early on in the natural history of CHF and soon after myocardial infarction, and is proportional to the severity of heart failure. Whereas findings from animal experiments suggest that the progression of CHF is associated with a worsening neurohormonal profile, there are insufficient human data to draw similar conclusions. Nevertheless, most studies indicate that high levels of neurohormones are predictive of a poor prognosis. ACE inhibitors reduce mortality in all stages of CHF, and the greatest benefit is seen in patients with the highest baseline level of neurohormones. Although data from the major randomized trials do not, as yet, support the hypothesis that ACE inhibitors act primarily through reduction of the levels of circulating neurohormones, other, indirect, data suggest that the progression of heart failure is related to excessive neurohormonal activation...