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Hyponatremia is independently associated with adverse outcomes in patients with congestive heart failure (CHF). The primary cause of hyponatremia in CHF is the inappropriate secretion of the antidiuretic hormone arginine vasopressin (AVP). The binding of AVP to V2 receptors in the renal collecting duct promotes water retention, a process that can lead to dilutional hyponatremia as well as increased ventricular preload. Conventional treatment of hyponatremia in CHF is largely based on water restriction, which is neither effective nor well-tolerated. V2- and dual V1a/V2-receptor antagonists offer physiologically based treatment for dilutional hyponatremia. Clinical trials in patients with hyponatremia including those with CHF using both selective and nonselective vasopressin antagonists have demonstrated the effectiveness and safety of these agents in correcting this common electrolyte abnormality. Congest Heart Fail. 2010;16(4)(suppl 1):S15–S18. ©2010 Wiley Periodicals, Inc.