Heart failure (HF) is a syndrome characterized by upregulation of the sympathetic nervous system and abnormal responsiveness of the parasympathetic nervous system. Studies in the 1980s and 1990s demonstrated that inhibition of the renin-angiotensin-aldosterone system with angiotensin-converting enzyme inhibitors improved symptoms and mortality in HF resulting from systolic dysfunction, thus providing a framework to consider the use of beta-blockers for HF therapy, contrary to the prevailing wisdom of the time. Against this backdrop, this article reviews the contemporary understanding of the sympathetic nervous system and the failing heart.