Heart failure constitutes a significant source of morbidity and mortality in the United States, and its incidence and prevalence continue to grow, increasing its burden on the health care system. Renal dysfunction in patients with heart failure is common and has been associated with adverse clinical outcomes. This complex interaction is characterized by a pathophysiological disequilibrium between the heart and the kidney, in which cardiac malfunction promotes renal impairment, which in turn feeds back, resulting in further deterioration of cardiovascular function. Multiple neurohumoral and hemodynamic mechanisms are involved in this cardiorenal dyshomeostasis, including resistance to compensatory cardiac natriuretic peptides, leading to sodium retention, volume overload, and organ remodeling. Previous studies in animal models of heart failure have demonstrated that renal denervation promotes a robust natriuresis and diuresis as well as increased response of endogenous and exogenous natriuretic agents. With the recent development of minimally invasive renal denervation in humans, it is possible to suggest that this technique may become effective and important in the management of renal sodium and water metabolism in heart failure.