This special issue aims to focus on some of the major scientific problems of its field.

It provides an up-to-date vision of:

• the current prion fundamentals, from the nature of the infectious agent to the species barrier phenomenon,
• the extraordinary progress – and also the limits – of the methodology to investigate the TSE agents,
• the rational, success and limits of genetic selection,
• and finally the current situation and future perspective of emerging TSE agents.