The syndrome of clinical heart failure (CHF) is characterized by increased activity of the sympathetic nervous system (SNS), which may contribute in part to the heightened vascular tone that adversely affects left ventricular systolic performance. The increased resting SNS activity is accompanied by an attenuated SNS response to physiological stress, including orthostasis, hypotension, and maximal exercise. Since heart transplantation appears to reverse the increased resting activity and the deficient reflex responsiveness, these abnormalities appear to be functional. The degree of SNS activation appears to be directly related to mortality in CHF, thus suggesting that heightened SNS activity is either a marker or a risk factor for a lethal outcome in this syndrome. Pharmacologic inhibition of the SNS is an attractive therapeutic option for evaluation in CHF.