Heart failure (HF) is still one of the most important causes of morbidity and mortality worldwide. Neurohormonal changes appear to play an important role in the development and continuation of HF. Among the mediators responsible for these changes, antidiuretic hormone (ADH) is probably the least known. However, elevated concentrations of ADH are frequently found in this syndrome and have prognostic value in addition to known biomarkers. Recent experimental studies and clinical trials have aroused interest in the possible benefits of ADH receptor antagonists. This article reviews the pathophysiological mechanisms of ADH in HF and the latest advances in ADH antagonism in the therapeutic management of HF.