Neurohormonal imbalances clearly contribute to the pathophysiology of chronic congestive heart failure. Agents that interfere with the generation or effects of angiotensin II and aldosterone, or which block the effects of excess sympathetic drive, all favorably affect mortality. Arginine vasopressin, through its V1A and V2 receptor-mediated effects, could theoretically also contribute to progression of left ventricular dysfunction and heart failure by aggravating systolic and diastolic wall stress, and by directly stimulating myocardial hypertrophy. Arginine vasopressin levels are increased in congestive heart failure patients; acutely, both V1A and V2 antagonists produce beneficial hemodynamic responses in both clinical and experimental congestive heart failure. Experimental studies also indicate beneficial effects of V1A and V2 antagonists (alone or in combination) on hemodynamics and possibly ventricular remodeling after myocardial injury. Currently, there are no long-term studies of any type of arginine vasopressin antagonist in human heart failure, but both the theoretical rationale and preclinical data would appear to justify such efforts.