Congestive heart failure is a major clinical and public health challenge. With increased aging, and advanced care of almost all other cardiac diseases, myocardial failure has become the single most common reason for hospitalization for patients older than 65. Conventional wisdom addressed heart failure as a hemodynamic perturbation consisting of congestion and limited cardiac output. Efforts intuitively focused on augmenting systolic function and clearing excessive pulmonary and systemic edema. Despite symptomatic improvement, mortality and functional deterioration continued unabated. Afterload reducing therapy emerged as an effective modality of improving cardiac function. Selective targeting of renin-angiotensin-aldosterone system (RAAS) was shown to be superior to alternative nonhormone-based approaches. These clinical observations gave impetus to the neurohumoral paradigm of heart failure. Whereas attention to the congestive aspects of heart failure remains an essential component of therapy, it is by no means sufficient to neutralize the complex and interactive pathogenic mechanisms which underlie this syndrome. Particularly relevant, is the asymptomatic stage of ventricular dysfunction which portend significant future structural and functional deterioration. Mounting evidence confirm the benefit of ACEI and ARB in attenuating ventricular remodeling and improving survival. This paper aims at reviewing the evidence which has led to the strongly held paradigm of neurohormonal basis of heart failure. Appropriate and evidence based therapeutic strategies are presented.