Diuretic resistance in patients with congesting heart failure is for the most part due to pharmacodynamic factors related to increased reabsorption of solute at other parts of the nephron. This mechanism explains the rationale for using combinations of diuretic agents affecting solute reabsorption at different nephron sites in such patients in contrast to a strategy of escalation of loop diuretic doses. Understanding the mechanisms by which diuretic resistance occurs in patients with CHF has allowed design of appropriate dosing regimens of these drugs and rational use of combinations of diuretics.