The conflicting results of diuretic treatments in heart failure (HF) and the importance of Na management in the context of the cardiorenal syndrome and neurohormonal activation in HF have suggested novel and counterintuitive strategies, focused primarily on the use of vasopressin antagonists and hypertonic saline solution with high doses of loop diuretics and their neurohormonal interference. The emerging novel therapies involving direct inhibition of vasopressin receptors appear to show promising results. The use of hypertonic saline solution mixed with a high dose of loop diuretics produces, probably by indirect mechanisms, a reduction or inhibition of the activated neurohormonal systems in HF patients. This treatment opens a new window on the role of sodium management in these patients and on the relation between sodium and the kidney's role and function in heart failure. The authors review the current evidence for these therapies and suggest hypothetical bases for their efficacy.