has in turn been ascribed to the unique sympatholytic properties of bucindolol. 7 Therefore, the harmful effects of sympatholysis are observed when a “pure” agent, such as moxonidine, is used to treat advanced heart failure patients, as well as when an otherwise beneficial, mixed action agent, such as bucindolol, is used in subpopulations who are predisposed to adverse effects of adrenergic withdrawal. The likely explanation for the polar difference in the response of these two general classes of antiadrenergic agents is that during the crucial early period of adrenergic inhibition, sympatholytic agents produce an irreversible removal of adrenergic support with the inability to recruit adrenergic drive when needed to support cardiac function. In contrast, ß-blockers are mass-action agents whose inhibition can be easily reversed by norepinephrine competition, which allows for the retention and recruitment of the powerful adrenergic support mechanism on an as needed basis. Extensions of these observations include the potentially favorable effects of therapeutic approaches that allow the beneficial aspects of adrenergic inotropic support to be maintained in the presence of ß-blockade, 10 or the addition to ß-blockade of positively inotropic device therapy.