The once-heretical concept that a misfolded protein is the infectious agent responsible for prion diseases is now widely accepted. Recent exciting research has led not only to the end of the skepticism that proteins can transmit disease but also to expanding the concept that transmissible proteins might be at the root of some of the most prevalent human illnesses. At the same time, the idea that biological information can be transmitted by propagation of protein (mis)folding raises the possibility that heritable protein agents may be operating as epigenetic factors in normal biological functions and participating in evolutionary adaptation.