Iron deficiency and heart failure frequently co-occur, sparking clinical research into the role of iron repletion in this condition over the last 20 years. Although early nonrandomized studies and subsequent moderate-sized randomized controlled trials showed an improvement in symptoms and functional metrics with the use of intravenous iron, 3 recent larger trials powered to detect a difference in hard cardiovascular outcomes failed to meet their primary endpoints. Additionally, there are potential concerns related to side effects from intravenous iron, both in the short and long term. This review discusses the basics of iron biology and regulation, the diagnostic criteria for iron deficiency and the clinical evidence for intravenous iron in heart failure, safety concerns, and alternative therapies. We also make practical suggestions for the management of patients with iron deficiency and heart failure and outline key areas in need of future research. Display omitted •Iron deficiency and heart failure frequently occur concurrently and are associated with adverse cardiovascular outcomes.•Early trials of intravenous iron repletion in patients with heart failure found improvements in symptoms and functional capacity, but subsequent large trials failed to confirm objective consistent benefit.•Side effects of and alternatives to intravenous iron repletion warrant careful consideration.