Prion diseases are a group of neurodegenerative diseases that affect mammals, including humans and ruminants such as sheep. They are believed to be caused by the conversion of the prion protein (PrP), a host expressed protein, into a toxic form (PrP(sc)). PrP(sc) accumulates in the brain, resulting in neuronal loss and the typical spongiform appearance of the brain. So far, there are no effective therapies available for prion diseases. This review discusses possible therapies for prion diseases and the models available for advancing research into the disease.