The important neuroendocrine systems implicated in heart failure are reviewed here, with special emphasis on their possible role in path pathophysiology and the chances of pharmacological intervention. The part played by the sympathetic nervous system and the renin-angiotensin-aldosterone system and the beneficial effects of β-blockers, ACE inhibitors, and angiotensin II antagonists are well-established. The involvement of vasopressin, endothelin-1, ANP, BNP, and TNF-α and the interventional possibilities relating to these hormones are also discussed. It is concluded that, in addition to the known interventional principles of neuroendocrine activation, there is a series of new exciting principles and some of them might become important in the future.