For a small proportion of the UK population, life can only be sustained through regular transfusions of blood. Such is the reality for the ~600 people living with thalassaemia major and ~200–300 living with conditions such as Diamond–Blackfan anaemia (DBA), congenital dyserythropoietic anaemia (CDA), congenital sideroblastic anaemia (CSA) and other rare inherited anaemias.1 For this small group of individuals, transfusions alone extend survival from the first weeks or months after birth, to approximately the first or second decades. Without further intervention, death inevitably follows at the hands of heart failure and liver cirrhosis, direct complications of iron, derived from the transfused erythrocytes, accumulating in the tissues.2 Having evolved as a species that can only regulate iron by choosing to absorb it or not, receiving iron parenterally poses a problem that our physiology cannot solve. Toxic iron overload is addressed by pharmacological intervention instead, one which takes the shape of ‘lobster-like claws’, the iron chelators. Between these molecular claws lies the iron, snatched from their natural iron-carrying proteins or directly from tissues, to then be excreted via the urine, faeces or both. The first chelator to be used in clinical practice was desferrioxamine.3 Initially given through the intramuscular route — a painful and disfiguring necessity endured by an early cohort of stoical thalassaemia patients — the development of a subcutaneous formulation revolutionised the quality of life and outcomes for patients with transfusion-dependent thalassaemia (TDT). While the search for the perfect oral chelator has not yet yielded a replacement with perfect pharmacokinetics and devoid of side effects, both deferiprone and deferasirox are widely available and, if used consistently by patients, should prevent any iron from accumulating in the tissues. Would that this should suffice. However, the complexities of caring for patients with transfusion-dependent anaemias result from a mixture of biological reasons and human factors. The guidelines from Shah et al., on the monitoring and management of iron overload in patients with haemoglobinopathies and rare anaemias, for the first time summarise our current understanding of the available evidence on chelation as best applied to each type of anaemia. These guidelines represent a resource likely to benefit far more than UK patients, but also those all over the world whose clinicians will welcome the clear advice. Patients with non-transfusion-dependent thalassaemia, CSA and CDA can all iron load through uncontrolled absorption of dietary iron. The ineffective erythropoiesis that is shared by these conditions is characterised by a very high level of immature erythroid precursors in the marrow. These EPO-stimulated cells are programmed to secrete high levels of Erfe (erythroferrone), the soluble hormone that powerfully suppresses hepcidin production.4 As a result, hepcidin transcription is repressed, leaving the ferroportin doors in the intestine wide open for iron to be absorbed into the bloodstream, and inevitably deposited into tissues in the absence of chelation. Even transfusion-dependent anaemias iron load at different rates. For equal amounts of blood transfused, patients with DBA will have worse tissue iron loading than patients with TDT.5 The culprit here is once again the bone marrow erythroblasts. While in TDT the erythroblasts will not yield useful mature red cells, at least the immature forms in the marrow are covered with transferrin receptors that can ‘mop up’ some of the iron inevitably derived from each unit transfused.6 For patients with DBA, a complete lack of erythroid precursors in the marrow puts the peripheral tissues at repeated additional exposure to non-transferrin-bound iron (NTBI), the most dangerous form of iron. Much to our frustration, there isn’t a single way of reliably keeping track of the precise level of iron accumulation in patients with iron overload. Serum ferritin, a simple blood test, is not only subject to interference from infection/inflammation, but also becomes unreliable once tissue iron loading has reached a certain limit. Thankfully the days of routine liver biopsies are in the past, and clinicians can choose between several magnetic resonance imaging (MRI)-based assessments of tissue iron loading. What is the best method? How often should patients be scanned? Shah et al. clearly outline the options and suggest pragmatic intervals depending on the type of anaemia and the degree of chelation, but the best method is the one which is available, the one the patient will attend and, importantly, the one that was used previously so that serial measurements can be obtained. Here again, one size does not fit all — while a cut-off of ferritin >1 000 μg/l is a good rule of thumb for when to start scanning patients, in people with CSA, where the cause of the anaemia is disruption in the haem synthetic pathway itself, cardiac iron loading can occur with ferritins in the range of 500–1 000 μg/l. Understanding why iron accumulates, which patients should be monitored and how often, and having access to well-tolerated chelators is not enough to ensure transfusion-dependent patients no longer become diabetic, suffer growth failure and other endocrinopathies, develop cirrhosis or die of heart failure. Cardiac T2*MRI values below 10 ms that give haematologists palpitations when they open the report, and rescue chelation needing to be given 24 h a day intravenously through a central line, are sadly not yet confined to the history books. So why can’t we protect our patients from developing iron overload? Here enter the human factors. As any clinician looking after people with lifelong conditions knows, compliance, now perhaps euphemistically renamed ‘concordance’ is, understandably, always an issue, especially around adolescence and the early adult years. The current guidelines do recommend altering scanning schedules in patients with poor compliance, but provide no insight as to how this can be improved. Here I would suggest we reach out to our nursing and psychology colleagues, and approach this with creativity, humility, and skills rooted in motivational interviewing and the Transtheoretical Model of Change.7 With the current well-tolerated and effective chelators available, and with accurate non-invasive monitoring techniques at our disposal, it now becomes imperative that we should partner with our patients and work out together how best to present treatment regimens in the context of the values that matter to them, and the lives they wish to live.