Chapter 1 lays the groundwork for the rest of the book by addressing the emergence of plague in the port city of Marseilles and its spread into southeastern France. It tells the story of the Grand Saint-Antoine, the infamous vessel that allegedly transported the plague to France from the Levant in 1720. It then situates this traditional narrative within the context of recent genetic studies that call its accuracy into question. Although the science has not yet been able to disprove the accepted historical explanation for the outbreak – which is to say, that the pathogen arrived on the ill-fated vessel – it has offered a valuable opportunity to revisit traditional understandings of disease as a product of the “orient,” and to examine and appreciate the influence of new technologies – in this case, genomic DNA analysis – on historical research and our interpretations of archival documents. The chapter moves on to discuss civil and religious responses to the epidemic and what I argue was the implementation of disaster centralism in France, as authorities in Paris stepped in to mitigate the threat of infection from Provence before it spread any further.