Cardiorenal syndrome describes the impairment of renal function and associated diuretic resistance in patients with heart failure and clinically manifest volume overload. The pathophysiology of this syndrome is poorly understood, but appears to be caused by impairment of tubuloglomerular feedback, neurohormonal activation, and other factors and therapies used in the management of heart failure. Early diagnosis of the cardiorenal syndrome by way of markers of renal injury and function is critical for timely interventions that may attenuate progression. Many novel therapies have been evaluated in the cardiorenal syndrome setting, including agents that block key local factors (eg, adenosine A(I) receptor antagonists), improve diuresis, aquaresis, and natriuresis, and augment natural vasodilator mechanisms to improve renal perfusion. Furthermore, device-based approaches such as ultrafiltration may also play an important therapeutic role.