Background: 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 interaction, termed the cardiorenal syndrome, is a complex phenomenon characterized by a pathophysiological disequilibrium between the heart and the kidney, in which malfunction of one organ subsequently promotes the impairment of the other. Multiple neuro-humoral mechanisms are involved in this cardiorenal interaction, including the deficiency of and/or resistance to compensatory natriuretic peptides, leading to sodium retention, volume overload and organ remodeling. Management of patients with the cardiorenal syndrome can be challenging and should be individualized. Emerging therapies must address the function of both organs in order to secure better clinical outcomes. To this end, a multidisciplinary approach is recommended to achieve optimal results.