Human diseases are not distributed at random geographically or temporally. The present chapter reviews how pathogens (infectious agents that cause disease) of humans have changed over evolutionary and historical times. Modern humans have been parasitized by the infectious agents of our earlier hominin ancestors, or by acquiring them from wild or domesticated animal species according to several epidemiological transitions: (1) the "out of Africa" source where pathogens followed the dispersal and expansion of modern humans and earlier hominins from Africa, as humans acquired new parasites and pathogens during the geographic expansion process (but also immune genes to cope with these new parasites by interbreeding with archaic humans); (2) the "domestication" source where pathogens spread from domesticated animals and then dispersed more globally; and (3) the "globalization" source, with expansion of pathogens in relation to historical and recent trade routes. Ongoing environmental changes result in both the emergence of news infectious diseases and the loss in parasite diversity, with striking consequences that include the rise of autoimmune diseases as well as zoonotic pathogens.