Infectious diseases and epidemics have always accompanied and characterized human history, representing one of the main causes of death. Even today, despite progress in sanitation and medical research, infections are estimated to account for about 15% of deaths. The hypothesis whereby infectious diseases have been acting as a powerful selective pressure was formulated long ago, but it was not until the availability of large-scale genetic data and the development of novel methods to study molecular evolution that we could assess how pervasively infectious agents have shaped human genetic diversity. Indeed, recent evidences indicated that among the diverse environmental factors that acted as selective pressures during the evolution of our species, pathogen load had the strongest influence. Beside the textbook example of the major histocompatibility complex, selection signatures left by pathogen-exerted pressure can be identified at several human loci, including genes not directly involved in immune response. In the future, high-throughput technologies and the availability of genetic data from different populations are likely to provide novel insights into the evolutionary relationships between the human host and its pathogens. Hopefully, this will help identify the genetic determinants modulating the susceptibility to infectious diseases and will translate into new treatment strategies. 1. Infections: A Scourge throughout Human History Infectious diseases and epidemics have always accompanied and characterized human history, representing one of the main causes of death. Even today, despite progress in sanitation and medical research, infectious diseases represented a major killer; data published by the World Health Organization (WHO 2008, http://www.who.int/en/) indicate that about 15% of deaths in the world's population are due to infectious and parasitic diseases, reaching about 41% in Africa. In the most recently published report (November 2012), the WHO estimated that in 2011 about 4.4 millions of children younger than 5 years died of infection. Anatomically modern humans appeared in East Africa about 200,000 years ago, spread out from sub-Saharan Africa approximately 100,000 years ago, and subsequently colonized the rest of the world in a series of migratory events [1]. During this process, humans not only encountered a wide range of different environmental conditions, including diverse pathogen species, but also introduced changes in subsistence strategies that allowed the development of large, interconnected societies. Hunter/gatherer communities
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