The United States is currently beleaguered by twin epidemics, heart failure (HF) and renal insufficiency (RI). HF and RI frequently coexist in the same patient, and this conjunction, often called the "cardiorenal syndrome," has important therapeutic and prognostic implications. Approximately 60% to 80% of patients hospitalized for HF have at least stage III renal dysfunction as defined by the National Kidney Foundation (NKF), and this comorbid RI is associated with significantly increased morbidity and mortality risk. Numerous studies have demonstrated that in patients with HF, indices of renal function are the most powerful independent mortality risk predictors. Comorbid RI can result from both intrinsic renal disease and inadequate renal perfusion. Atherosclerosis, renal vascular disease, diabetes mellitus, and hypertension are significant precursors of both HF and RI. Moreover, diminished renal perfusion is frequently a consequence of the hemodynamic changes associated with HF and its treatment. Both HF and RI stimulate neurohormonal activation, increasing both preload and afterload and reducing cardiac output. Inotropic agents augment this neurohormonal activation. In addition, diuretics can produce hypovolemia and intravenous vasodilators can cause hypotension, further diminishing renal perfusion. Management of these patients requires successfully negotiating the delicate balance between adequate volume reduction and worsening renal function. Despite this, few evidence-based data are available to guide management decisions, indicating a compelling need for additional studies in this patient population.