Hyponatremia is the most common electrolyte disorder encountered in the clinical setting. Abnormalities of the mechanisms that maintain normal water and sodium metabolism are often present in hospitalized patients, including defects in renal water excretion. All of the current therapeutic approaches in patients with the syndrome of inappropriate antidiuretic hormone secretion and other forms of vasopressin-induced hyponatremia have significant limitations. Studies in animal models and humans have demonstrated that antagonists of the AVP V2 receptor in the kidney are effective in correcting hyponatremia. These new agents have been termed "aquaretics" because of their ability to induce a free water diuresis without the natriuresis or kaliuresis characteristic of diuretic drugs. When approved for clinical use, selective V2, and possibly also combined V1 + V2 receptor antagonists will be helpful in therapy.