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The data of diuretics are still controversial. The ability to induce negative fluid balance has made diuretics useful in the treatment of a variety of conditions, particularly edematous states as heart failure (HF). At the beginning of 1940, only three drugs were accepted as effective agents to increase urine flow: caffeine (a mild diuretic), digitalis (a potent agent but useful only in HF), and mercury (despite its improvement as an organomercurial remained potentially a toxic one). In the late 1950s and 1960s, a significant breakthrough was achieved with the discovery of chlorothiazide and furosemide.1,2 Since them, diuretics have been the cornerstone for treatment of both acute and chronic HF, with signs and symptoms of congestion (NYHA II-IV), irrespective of ejection fraction (EF). They clearly improve hemodynamics and symptoms, although many studies have not been able to demonstrate a mortality benefit. A recent meta-analysis of a few small trials found that diuretics were associated with a reduction in mortality as well as reduced admission for worsening HF. In Croatia, we routinely used all four groups of diuretics diminishing sodium reabsorption at different sites in the nephron, thereby increasing urinary sodium and water losses. Examples of loop diuretics include: furosemide, torsemide. Examples of thiazide diuretics include: chlorthalidone, hydrochlorothiazide, indapamide. Examples of potassiumsparing diuretics include: spironolactone, eplerenone. Loop diuretics act in the thick ascending limb of the loop of Henle. The bioavailability of furosemide is extremely variable (10-90%). The bioavailability can be improved if it is taken before meals because food can disrupt its absorption. Furosemide is absorbed from the gastrointestinal tract, and its peak diuretic effect occurs between 1 and 1.5 hours after oral administration, and between 10 and 30 minutes after intravenous (iv.) administration. The half-life of the various loop diuretics are not the same: 1-1.5 hours for furosemide and 3-4 hours for torsemide. The half-life of furosemide is prolonged in advanced renal dysfunction, and the half-life of torsemide is doubled in hepatic dysfunction. Because diuretics acutely decrease left ventricular preload (Figure 1), they can lead to a reflex neurohormonal stimula- tion of the sympathetic nervous system and renin-angiotensin-aldosterone axis. Numerous studies have determined that activation of these pathways contributes to the pathophysiology of HF, thus potentially undermining the benefits of diuretic use. That is the reason why furosemide occasionally needs to be administered two or three times a day or in 24-hour infusion.1 Concurrent treatment with neurohormonal blockade (i.e., vasodilators, beta blockers, renin-angiotensin-aldosterone system antagonists) may improve outcomes. In patients with severe edema, the effect of furosemide may be altered due to inadequate gastrointestinal absorption. Patients unresponsive to oral furosemide should be switched to iv. therapy or oral torsemide. The bioavailability of torsemide is predictable. It is extremely well absorbed (80-90%), regardless of the presence of edema, because it undergoes substantial hepatic elimination. Torsemide can be administered once daily 5-20mg. The dosage of iv. administered furosemide is usually half of the oral dose. Furosemide is started with 20mg and can be incremented up to 40mg according to the diuretic response. Maximum single oral doses of furosemide for patients with normal glomerular filtration range from 40 to 80mg and the maximum daily dose is 600mg. If the maximum dose has already been given, it is recommended to increase the frequency of the dose to 2 or 3 times a day. Thiazide diuretics are most commonly used to treat hypertension, although they can be adjuncts in the management of HF. Adjunctive use of thiazides can overcome the resistance to loop diuretics associated with reactive hypertrophy of the distal convoluted tubule of the nephron. They inhibit the Na-Cl symporter in the distal convoluted tubule, leading to decreased sodium and water reabsorption. Spironolactone inhibits the aldosterone receptor in the cortical collecting duct, also limiting sodium and water reabsorption. Its diuretic effect is relatively weak, and its onset of action is slow. To conclude, diuretics are well established as the first-line therapy for HF patients with congestion. Since every patient represents a single entity and may have different responses to the same treatment, the best clinical approach should take into account physical examination, neuro-hormonal overdrive and kidney functional status. [ABSTRACT FROM AUTHOR]