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It is a common assumption that – compared with the Mesolithic – the adoption of Neolithic lifeways was accompanied by a higher risk of infection and the development of epidemic diseases. Such a hypothesis seems plausible when considering singular archaeological parameters like increasing population density and palaeopathological indicators of poor health. However, evidence for the far-reaching consequences of epidemics has not yet been examined. Thus, the relevance of infectious diseases as triggers for transformation processes in the Neolithic remains to be identified. By reviewing specific archaeological, genetic and palaeopathological proxies gained from groups of individuals that inhabited the German loess zone from the early to the final Neolithic, we provide a diachronic view of the periods between 5500 and 2500 BCE with regard to postulated indicators of epidemic events. Our analyses of the archaeological proxies suggest major transformations in domestic strategies and mortuary practices, especially in the middle and late Neolithic. Interestingly, mass burials indicative of epidemic events are lacking. Ancient DNA results on pathogens confirm single infections throughout the Neolithic, but there is no clear evidence for diseases of epidemic proportions. The osteological records are not conclusive since the majority of osseous changes are unspecific with regard to the cause and course of infections. We conclude that currently neither biological nor archaeological proxies suggest substantial contributions of epidemics to Neolithic transformations in the German loess zone. This finding contrasts with the general assumption of a higher risk of infection and the development of epidemic diseases during the Neolithic.