Acute decompensated heart failure accounts for more than 1 million hospitalizations in the USA every year. Currently, the most common treatment for symptom relief is the use of loop diuretics, despite recent concerns for potential adverse effects. With the growing understanding of the role of neurohormonal dysregulation in the pathophysiology of heart failure, there has been increasing interest in novel pharmacologic therapies targeting specific neurohormonal axes. Serum arginine vasopressin is a potent vasoconstrictor, as well as an antidiuretic, and serum concentrations are upregulated in heart failure. Tolvaptan, a vasopressin receptor antagonist, has been shown to improve diuresis and symptom relief without adversely affecting renal function, and may be a promising novel therapeutic agent in the growing population of patients with heart failure.