Bucindolol is a non-selective ߭adrenergic receptor blocker with a-1 blocker properties and mild intrinsic sympatholytic activity. The Beta-Blocker Evaluation of Survival Trial (BEST), which is the largest clinical trial of bucindolol in patients with heart failure, was terminated prematurely and failed to show an overall mortality benefit. However, benefits on cardiac mortality and re- hospitalization rates were observed in the BEST trial. Bucindolol has not shown benefits in African Americans, those with significantly low ejection fraction and those in NYHA class IV heart failure. These observations could be due to the exaggerated sympatholytic response to bucindolol in these sub-groups that may be mediated by genetic polymorphisms or changes in gene regulation.