Worsening renal function during the treatment of acute decompensated heart failure, so-called acute cardio-renal syndrome, is very common and complicates the treatment course. The underlying pathophysiology of worsening renal function (WRF) involves variable contributions of renal hemodynamics, neurohormonal activity, and oxidative stress. Historically, WRF has been associated with adverse outcomes. However, emerging data support therapeutic strategies that permit WRF while effectively treating congestion as they are associated with improved outcomes.