Both beta-blockers as well as positive inotropic drugs may be indicated for the treatment of patients with advanced or refractory heart failure. When tolerated, beta-blocker therapy is able to counteract the adverse biologic effects produced by the chronic activation of the sympathetic nervous system and, therefore, to delay the progression of the disease. Conversely, although the long-term administration of positive inotropic agents is not recommended, these drugs may be required to face episodes of acute hemodynamic deterioration, which frequently occur in patients who are so severely impaired. Beta-blocker and positive inotropic therapies are currently viewed as alternative strategies for the management of severe heart failure patients. However, both the theoretical background and preliminary clinical evidences about the combined use of these two drug classes are suggestive of the potential for cumulative benefits and of the mutual attenuation of deleterious effects.