Prion propagation is associated with accumulation of a conformational isomer of host encoded cellular prion protein, PrP(C). Solution structures of several mammalian PrPs have now been reported and they have stimulated a significant advance in our understanding of the folding dynamics of PrP. Studies on recombinant PrP have shown the polypeptide chain is able to adopt different topologies in different solvent conditions. Concomitantly, advances in the analysis of the abnormal isoform, PrP(Sc), have expanded our knowledge on the molecular basis of prion strains and have done much to reinforce the protein-only hypothesis of prion replication.