Would you believe that infectious disease can also be transmitted in the absence of the typical players like viruses, bacteria, or parasites? Scientists have been shocked to discover that proteins, comprising the fundamental structure and function of every living thing, could also be involved in transmissible disease. Malformed proteins, including prions, are the topic of this unit. The term “prion” was coined by Nobel Laureate Stanley Pruisner in 1982, as an acronym for “proteinaceous infectious particle”. Though the last two decades have revealed more about the peculiar behavior of these misshapen proteins, much remains unknown. Distinct from bacteria and viruses, prions continue to challenge our deep-seated biochemical assumptions about infectious disease.