Throughout the history of mankind, population migration has played an important role in determining a dynamic interplay of humans with other animals, plants, insects, and microbial agents in different ecological niches. In this journey, some microbes have negotiated symbiotic relationships with humans by achieving molecular and cellular compromises, ultimately sculpting the human genome. In other cases, many microbial agents have acted as pathogens and therefore becoming forces of natural selection throughout different human societies by leading to morbidity, dysfunction, or death. In this manner, the establishment of modern societies is in many ways the result of the burden of disease associated with infectious pathogens throughout millennia. Throughout the history of mankind, epidemics of infectious diseases have influenced political, economic and social aspects of human societies at least through the occurrence of four epidemiologic transitions: a) the Neolithic period with the establishment of the first human villages with enough population density enabling the spread of infectious agents; b) the middle-ages with the spread of bubonic plague causing important demographic changes; c) the worldwide exploration of European with colonization in new territories; and d) the current era of globalization. In summary, there is an inextricable link between humanity’s journey and microorganisms resulting in either beneficial or antagonistic interactions