An excessive amount of iron may become extremely toxic both for its ability to generate reactive oxygen species, and for the lack of regulatory mechanisms for iron excretion in humans. Chelation therapy has been introduced in clinical practice in the 1970′s to defend thalassemia patients from the effects of iron overload and it has dramatically changed both life expectancy and quality of life. The disadvantages of the drugs in clinical use make the research for new, more suitable iron chelating agents, urgent. This review defines the requirements of an iron chelator, then points out the principal chemical features of the iron chelators in use. Finally, a survey on the last ten years of the literature relative to iron chelators is done, and the most interesting ligands are presented, with particular emphasis to those that reached clinical trials.