Prion diseases are fatal infectious neurodegenerative disorders; examples include the Creutzfeldt-Jakob disease affecting humans and bovine spongiform encephalopathy in cattle. The causative agents of these diseases--the prions--are thought to consist of the pathogenic isoform of the prion protein PrP(Sc), which is produced by the conformational conversion of the normal isoform PrP(c). Many lines of evidence indicate that the constitutive conversion of PrP(c) to PrP(Sc), resulting in a marked accumulation of PrP(Sc) in the brain, is a central event in the pathogenesis of prion diseases. A large number of compounds have been identified as anti-prion agents and capable of reducing the PrP(Sc) levels in infected cells. Some of these compounds have been found to be partially effective in infected animals, thus resulting in the prolongation of the incubation or survival times and a few of these compounds were or are under clinical trials. However, none of these compounds have proven to be therapeutically effective against this group of diseases. This is probably because (1) these compounds fail to cross the blood-brain barrier and (2) their effectiveness is reduced because they are administered only to patients with clinically advanced disease owing to a lack of diagnostic indicators for presymptomatic individuals. In this communication, we systematically list these anti-prion compounds and summarize their effectiveness and possible mechanisms of action.