Despite known sex differences in pharmacokinetics and pharmacodynamics, the target dosages for heart failure medication recommended by international guidelines are the same for both men and women. In a recent post-hoc analysis in The Lancet, Santema and colleagues evaluated sex-based differences in clinical outcomes related to the dosage of three classes of heart failure drugs. They found that women may reach the peak benefit of angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and β blockers at half the recommended target dosage. This commentary discusses the study by Santema and colleagues and its implications for clinical practice.