The clinical pharmacology of torasemide, bumetanide, piretanide and furosemide (frusemide) is discussed. These drugs share a similar mechanism of action in inhibiting Na(+)-K(+)-2Cl- reabsorption at the thick ascending limb of the loop of Henle. They differ in their routes of metabolism, pharmacokinetics, and potency. Whether such differences are clinically important requires further study. Bumetanide and torasemide are metabolised by cytochrome P450 pathways, whereas furosemide is glucuronidated. These different routes of metabolism may have clinically important implications. Bumetanide, furosemide, and piretanide have similar pharmacokinetics, whereas the clearance of torasemide is less and the half-life concomitantly longer than the other 3 agents. Thus, torasemide has a longer duration of action. The rank order of potency is bumetanide greater than piretanide identical to torasemide greater than furosemide, although efficacy appears the same. Despite much being known about these diuretics, many clinically important questions remain.