Heart failure is a complex clinical syndrome, and only part of this syndrome is based on the mechanical failure of the heart muscle itself to provide sufficient systemic perfusion. Heart failure is accompanied by the activation of various immunologic and neurohumoral mechanisms. These may be intended by nature to be physiologically beneficial, but eventually become deleterious as they provoke ischemic, proarrhythmic, vascular, and structural changes in the myocardium that contribute to the versatile symptoms of the heart failure syndrome. Today's concept of the pathogenesis of heart failure regards heart failure as a dynamic state influenced by at least 2 major mechanisms, namely "neurohumoral" activation and ventricular remodeling. Progressive chronic heart failure can be viewed as a result of the prolonged impact of both pathogenetic mechanisms. This article will describe briefly the features of the neurohumoral forces on the pathogenesis of heart failure, including immunologic forces, which also influence the remodeling process.