The clinical success of neurohumoral manipulation by ACE inhibitors and beta blockers in heart failure has led to new therapeutic approaches. New neurohumoral factors are now viewed as offering the potential for treatment interventions. Not only do we consider blocking the production of deleterious hormones, but also, more recently, consideration has been given to augmenting the actions of factors with potentially beneficial actions. Hopefully such manipulation of ADM and ET-1 can result in further improvement in the well-being of heart failure patients.