Heart failure with reduced ejection fraction (HFrEF) is a clinical reality with an incidence of >10% in the population over 65 years of age, expected to increase in the coming years. Alongside the well-known pharmacological options (e.g. angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, neprilysin inhibitors, beta-blockers, aldosterone antagonists), which have significantly improved the clinical and prognostic outcomes of HFrEF patients, we now have a new therapeutic target: iron deficiency, defined as a ferritin concentration <100 μg/l or between 100-300 μg/l in the presence of a transferrin saturation <20%. Iron plays a major role in the transport of oxygen as a component of hemoglobin, as an oxygen reservoir, and as a component of myoglobin, as well as in the formation of energy, as a constituent of respiratory chain enzymes. Iron deficiency can therefore lead to anemia, changes in cognitive performance, behavior, emotions, reduced exercise capacity and myocardial structural and functional changes. Several clinical studies have shown that intravenous iron carboxymaltose supplementation can improve anemia, NYHA class, quality of life and exercise capacity of HFrEF patients. There are no randomized studies of adequate sample size that positively correlate iron supplementation with the higher endpoints of mortality and morbidity both in chronic and acute heart failure. Several studies are ongoing to answer these questions in the next few years.