.....Such a process is linked to the binding of metal ions (e.g., Cu, Fe and Zn) with Aβ. As a result, metal chelation could be used as a rational therapeutic pathway for the treatment of AD. In this review, we address some noteworthy advances on the utilization of metal chelators, such as native metallothioneins and synthetic compounds, as potential therapeutic agents for AD. In addition, the future design and utility of metal chelating drugs as well as the strategy pursued to transport metal chelators into the brain are highlighted. We believe that this contribution will be valuable for the design of metal-chelating drugs for AD treatment.