The pathological foundation of human prion diseases is a result of the conversion of the physiological form of prion protein (PrP©) to the pathological protease resistance form PrP(res). Most patients with prion disease have unknown reasons for this conversion and the subsequent development of a devastating neurodegenerative disorder. The conversion of PrP© to PrP(res), with resultant propagation and accumulation results in neuronal death and amyloidogenesis. However, with increasing understanding of neurodegenerative processes it appears that protein-misfolding and subsequent propagation of these rouge proteins, is a generic phenomenon shared with diseases caused by tau, alpha-synucleins and beta-amyloid proteins. Consequently, effective anti-prion agents may have wider implications. A number of therapeutic approaches include polyanionic, polycyclic drugs such as pentosan polysulfate (PPS), which prevent the conversion of PrP© to PrP(res) and might also sequester and down-regulate PrP(res). Polyanionic compounds might also help to clear PrP(res). Treatments aimed at the laminin receptor, which is an important accessory molecule in the conversion of PrP© to PrP(res) - neuroprotection, immunotherapy, siRNA and antisense approaches have provided some experimental promise.