Early and regular blood transfusion therapy in patients with homozygous β‐thalassaemia decreases the complications of severe anaemia and prolongs survival. In the long term, however, the beneficial effects of transfusions are limited by the organ damage resulting from iron overload, a consequence of the body's limited capacity to excrete iron, and by the complications of infection with blood‐borne agents. Transfusion regimens for β‐thalassaemia have changed substantially during the past four decades. In current protocols, pre‐transfusion haemoglobin concentration should not exceed 95 g/l. This allows adequate control of anaemia, with a relatively low rate of iron accumulation. Although iron chelation therapy has successfully improved survival free from cardiac disease, thalassaemic patients continuously present new clinical challenges. In fact, the vast majority of them suffer from post‐transfusion chronic hepatitis C, which is expected to significantly contribute to morbidity in the forthcoming years. Furthermore, recent studies demonstrated that thalassaemics are at high risk of acquiring several blood‐borne viruses. The potential role of these multiple infections in inducing clinical disease is still uncertain, and needs to be thoroughly clarified in future surveys.