In patients with acute decompensated heart failure, worsening renal function during conventional decongestive therapy (cardiorenal syndrome) affects prognosis and the initiation of therapies with known benefit in chronic heart failure. Potential strategies for decongestion in patients who develop cardiorenal syndrome include invasive hemodynamic monitoring to guide therapy, use of continuous diuretic infusions, ultrafiltration, or novel therapy with adenosine or vasopressin receptor antagonists. Clinical trials by the National Heart, Lung, and Blood Institute's Heart Failure Network are currently underway to validate such therapies in patients with acute decompensated heart failure with worsening renal function and to establish novel biomarkers for the early identification of patients who develop cardiorenal syndrome.