Acute heart failure exacerbations center around volume overload and treatment of this disease process often requires aggressive diuresis in order to achieve symptomatic relief. The management of heart failure through the use of intravenous diuretics is at times limited due to renal function. An elevated Cr level, which has previously been associated with poor outcomes, is a common end-point in most AHF trials. However, recent data has called into question the validity of Cr as a marker of prognosis. The objective of this chapter is to review the mechanisms by which loop diuretics function, the efficacy of Cr as a marker of renal injury, potential novel markers, as well as alternative therapies to optimize decongestion in the setting of AHF.