A well established part of therapeutic approaches applying to cases of chronic heart failure (CHF) with extreme fluid retention is represented by intensive intravenous (i.v.) therapy with loop diuretics. This kind of therapy, if appropriately modulated according to the individual clinical picture and biohumoral pattern, is able to decrease the abnormally high ventricular filling pressures, thereby relieving the breathlessness while being able to retrieve a suitable urine output, so as to propitiate regression or disappearance of edema without unfavorable influences on renal clearance of nitrogenous compounds. Nevertheless, the intensive i.v. diuretic therapy should be tailored on the basis of a close assessment of baseline hemodynamic data and hemodynamic response to the medications, in addition to the careful diuretic dose titration and cautious evaluation of risk/benefit ratio. Actually, by using this kind of therapy, there is a risk that a tubular or glomerular injury can be generated and that a frequently preexisting renal dysfunction can be aggravated, especially when excessive doses of loop diuretics are being erroneously administered, so as to cause hypotension, hypoperfusion and/or relative dehydration in patients with decompensated CHF who could have expressly benefitted from intensive unloading therapy. Recently, the genesis of CHF-related progressive renal deterioration has been highlighted by affirming that a major role may be played rather by neurovegetative disorders, that is, by increase in sympathetic tone and abnormalities in kidney's vasomotility than by cardiac inotropism deficiency. The measures, thought to be able to prevent renal arterial constriction and to impede deterioration of glomerular filtration rate (GFR) due to the ischemic–necrotic tubular injury, as occurring in the set of intensive unloading therapy with i.v. furosemide or other loop diuretic, are represented by application of inotropic and renal vasodilator support by dopamine i.v. infusion at low doses or by other inotropic agents provided with recognized renal vasodilator properties and/or by addition to i.v. furosemide of osmotic agents able to expand the hematic volume, so counteracting or minimizing the reflex renal vasoconstriction induced by furosemide-related reduction in intravascular circulating volume: i.v. infusion of small volumes of hypertonic saline solution, as well as administration of albumin, mannitol and/or plasma expanders. Because renal impairment, as developing in the setting of CHF, has proven to represent a very important indicator of adverse outcome, every effort should be addressed to prevent any significant (>25% of basal value) rise in serum creatinine consequent to diuretic unloading therapy or to other procedures (paracentesis of tense ascites, ultrafiltration) aimed at rapid fluid removal in edematous or ascitic CHF or cardiogenetic anasarca. Ultrafiltration, even though a promising technique highly valued for its acknowledged property to obtain a more rapid fluid and weight loss in CHF patients with marked fluid retention, has been demonstrated so far to produce neurohumoral activation, creatinine abnormalities and symptomatic hypotensions similar to those due to i.v. loop diuretics; thus, the hypothesized advantages of this technique remain to be further clarified and confirmed, with regard to its safety profile and cost-effectiveness.