© 2018 The Authors. European Journal of Heart Failure © 2018 European Society of Cardiology Multiple drug classes have shown incremental benefits in heart failure with reduced ejection fraction. Most of these trials were designed to achieve specific doses of the investigational agent. Clinical practice guidelines recommend using the same target dosing of therapies, as tolerated. However, with the increasing number of available therapies, clinicians face the challenge of simultaneously using several drugs, achieving target doses, and managing side effects that are often overlapping. Blood pressure, renal function, hyperkalaemia, and other factors may impede achieving target doses of all medications, leaving clinicians with dilemmas as to how to sequence and dose these various classes of drugs. The guideline-directed eligibility for certain drugs and devices requires stability on maximally tolerated doses of background therapies. However, significant variability exists in dosing achieved in clinical practice. We discuss the existing background data regarding the doses of heart failure medications in clinical trials and in practice, and provide recommendations on how to navigate this complex therapeutic decision-making.