The prion protein is well known because of its association with prion diseases. These diseases, which include variant CJD, are unusual because they are neurodegenerative diseases that can be transferred between individuals experimentally. The prion protein is also widely known as a copper binding protein. The binding of copper to the prion protein is possibly necessary for its normal cellular function. The prion protein has also been suggested to bind other metals, and among these, manganese. Despite over ten years of research on manganese and prion disease, this interaction has often been dismissed or at best seen as a poor cousin to the involvement of copper. However, recent data has shown that manganese could stabilise prions in the environment and that chelation therapy specifically aimed at manganese can extend the life of animals with prion disease. This article reviews the evidence for a link between prions and manganese.