Treatment of congestive heart failure has changed dramatically during the past 20 years, but diuretic drugs remain an essential component. Diuretics are essential despite the fact that these drugs stimulate the renin-angiotensin-aldosterone (RAA) axis and lead to adaptive responses that may be counterproductive. In this paper, new diuretic drugs and new uses of older drugs are discussed. These approaches emphasize low-dose combination therapy and may prove superior to traditional approaches that rely exclusively on loop diuretics. Such approaches aim to prevent adverse compensatory processes that appear to result from chronic diuretic treatment. These include acute and chronic increases in plasma renin activity and stimulation of the sympathetic nervous system, both of which increase afterload and may tend to increase mortality. They also include adaptive changes in nephron structure and function resulting from diuretic-induced increases in distal sodium load and diuretic-induced neurohormonal stimulation. These adaptations blunt the effectiveness of diuretic therapy. Diuretic strategies that rely on combinations of diuretics are emphasized as a method to prevent resistance. If diuretic resistance does develop, higher-dose combination regimens, continuous diuretic infusions and mechanical ultrafiltration can be used to overcome diuretic adaptations and restore diuretic efficacy. The goal of reducing the extracellular fluid volume with the least stimulation of the RAA axis and minimal changes in nephron architecture can be achieved in many patients.