From a historical perspective, SARS-CoV-2 and COVID-19 have simultaneously led to known and previously unknown events as well. These seamlessly linked events can only be grasped with a new, integrative perspective of the relationship between culture and disease. Such a view requires a historiography that captures the full spectrum of an epidemic event, from the causes of emerging pathogens to their global spread and impact on different national, regional, and local communities. Integrative approaches to a global history of epidemics essentially include the following: –Understanding the dynamic relationship between nature and culture to empirically capture changes in local and regional biospheres and their interaction in global contexts. –Investigating the culturally determined scientific and social negotiation processes that lead to the naming, characterization and communication of initially unknown causes of disease in relation to the culturally determined countermeasures that begin with their emergence. –Analysis of the effects of worldwide densification through new technical possibilities and new forms of globally organised production and the associated traffic of trade, transport and communication in historical perspective. These empirical approaches represent nodes in a seamless web of interacting factors. Such an approach necessarily has to bring together a wide range of disciplines and perspectives.