β-blockers represent a mainstay in the pharmacological approach to patients affected by heart failure with reduced ejection fraction (HFrEF). However, underuse of this class of drugs is still reported, especially in the presence of cardiovascular and non-cardiovascular comorbidities, even if they are not contraindications for prescription of a β-blocker. The prognostic benefit of β-blockers is relevant in the presence of comorbidities, and achievement of the maximum tolerated dose is an important goal to increase their favorable prognostic role.