Iron is essential for the proper functioning of all living cells, however it is toxic when present in excess. Thus, using iron chelators as therapeutic agents, namely chelation therapy, has received increasing attention. The objective of this review is to discuss the factors which should be considered when designing clinically useful iron chelators, to present the application of iron chelators in the treatment of iron overload associated with β-thalassaemia major and sickle cell anaemia, and to highlight the potential applications in the treatment of neurodegenerative disorders and microbial infection. This article reviews recent knowledge centred on these themes and indicates the growing importance of the concept of iron chelation in medicine.