Over the past decade, small extracellular vesicles called exosomes have been observed to harbour protein and genetic cargo that can assist in health and also cause disease. Many groups are extensively investigating the mechanisms involved that regulate the trafficking and packaging of exosomal contents and how these processes may be deregulated in disease. Prion diseases are transmissible neurodegenerative disorders and are characterized by the presence of detectable misfolded prion proteins. The disease associated form of the prion protein can be found in exosomes and its transmissible properties have provided a reliable experimental read out that can be used to understand how exosomes and their cargo are involved in cell-cell communication and in the spread of prion diseases. This review reports on the current understanding of how exosomes are involved in the intercellular spread of infectious prions. Furthermore, we discuss how these principles are leading future investigations in developing new exosome based diagnostic tools and therapeutic drugs that could be applied to other neurodegenerative diseases.