Diuretics are the most commonly used drugs to treat clinically diagnosed fluid overload in patients with heart failure. There is no conclusive evidence that they alter major outcomes such as survival to hospital discharge or time in hospital compared to other therapies. However, they demonstrably achieve fluid removal in the majority of patients, restore dry body weight, improve the breathlessness of pulmonary edema and are unlikely to be subjected to a large double-blind randomized controlled trial in this setting because of lack of equipoise. The effective and safe use of diuretics requires physiological understanding of the pharmacokinetics and pharmacodynamics of diuretic therapy, an appreciation of the clinical goals of diuretic therapy, the application of physiological targeting of dose, an understanding of the effects of hemodynamic impairment on their ability to achieve fluid removal, an appreciation of the effects of combinations of different diuretics in patients refractory to single agents and an understanding of the most common side effects of such therapy. The use of continuous infusions of loop diuretics, sometimes combined with carbonic anhydrase inhibitors and/or aldosterone antagonists and/or thiazide diuretics can prove particularly effective in patients with advanced heart failure. Such therapy often requires more intensive monitoring than available in medical wards. If diuretic therapy fails to achieve its clinical goals, ultrafiltration by semipermeable membranes is reliably effective in achieving targeted fluid removal. The combination of diuretic therapy and/or ultrafiltration can achieve volume control in essentially all patients with heart failure.