Human and animal prion diseases are rare and fatal transmissible neurodegenerative disorders and correspond to a new host-agent interaction. So far, no infectious conventional agent has been isolated from brains of affected. These diseases are characterized by the accumulation in the central nervous system of an abnormal form of the prion protein (PrPc) which is a normal cell component. This abnormal form, PrPSc or PrPres, exhibiting a very high resistance to proteases, results from a conformational change of PrPc and would be an essential part of the transmissible agent, called prion, according to the concept developed by Prusiner since 1982. PrPc is expressed at the cell surface of neurons and peripheral tissues. All mammals studied so far encode PrP. Its tertiary structure has been recently established in part by nuclear magnetic resonance. Although its physiological role is still unknown, PrPc appears to be the receptor of the contaminating agent. Mice devoid of PrP have a normal development and behaviour but are resistant to the disease. Transgenic studies have demonstrated that the molecular basis of the host susceptibility is based in part on the primary structure of PrP. In mouse, sheep and human, different amino acid substitutions in the protein have been associated with opposite incubation times. The propagation of prions would result of a conformational imprinting imposed by infectious PrePres to host PrPc. The newly acquired conformation of the host protein would transmit to all neosynthetized PrPc in a autocatalytic process. Recently, evidence for the existence of different possible conformations of the abnormal protein could explain the variability of the agent strains. Recent data indicate that prion diseases would be the first transmissible disorders in which the information carried by the agent would be hidden in the tertiary structure of a protein and not in a nucleic acid. However, the virus hypothesis has not been totally discarded by some investigators.