Mammalian transmissible spongiform encephalopathies are likely due to the propagation of an abnormal form of a constitutive protein instead of traditional genetic material (nucleic acids). Such infectious proteins, which are termed prions, exist in yeast. They are at the origin of a number of phenotypes that are inherited in a non-Mendelian manner. These prions are very useful to dissect the molecular events at the origin of this structure-based inheritance. The properties of mammalian and yeast prions are presented and compared. This review highlights a number of similarities and differences.