Heart failure is a particularly complex disorder with etiology that is primary in nature or secondary to other systemic diseases, including hypertension, diabetes, and atherosclerosis. The pathogenesis appears to result, in part, from extensive abnormal interactions among tissues, such as the heart, vasculature, kidney, lungs, and sympathetic nervous system. Improvements in understanding this complex disorder, particularly factors that contribute to cardiac cell cycle alterations, gene activation and re-expression resulting in cardiac remodeling and, eventually, maladaption are paramount. Clinical experience with the current generation of mechanical blood pumps continues to be promising; nonetheless, these devices are not the definitive therapy for all patients with heart failure. The next generation of devices capable of mimicking many of the native heart pump attributes, such as responsiveness to preload, afterload, contractility, and beat rate, will broaden the use of this technology. In addition to solving the fundamental engineering challenges (size, energy supply, biocompatibility, durability, and portability), implantable heart pumps that are physiologically adaptive would enhance the treatment strategies for prolonged chronic support. The ultimate measure of device mediated success is to show improvements that extend beyond a favorable hemodynamic profile and include nutritional status and metabolic and neurohormonal levels and must demonstrate improved exercise tolerance and a better quality of life.