In 1975, the French historian Jean-Noël Biraben published what is still considered a monument in the historiography of plague: Les hommes et la peste en France et dans les pays européens et méditerranéens (Humans and Plague in France, Europe, and the Mediterranean). In recent years, Biraben’s data on close to 7,000 plague outbreaks in Europe have been digitized and used with increasing frequency by scientists, both biological and social, who wish to do “big data” analysis on one of the most lethal diseases in human history. However, Biraben’s data were hardly complete even when he published in the mid-1970s. His coverage reflected records he was able to access, and showed a heavy bias toward France and England. Biraben was, moreover, inevitably trapped in a “retrospective diagnosis” paradigm, inferring microbial processes from verbal descriptions made in a pre-microscopic age. Since the 1970s, molecular genetics, and particularly its latest subfield, paleogenetics, have made it possible to retrieve (and so to prove the presence of) plague and other infectious diseases in historical remains, stretching back thousands of years. There is now in place an evolutionary understanding of the causative organism of plague, Yersinia pestis, which links together every bacterium that has ever existed into one global narrative. And that narrative shows that although Y. pestis has existed for many thousands of years, the most significant phase of its history happened during the late Middle Ages and the early modern period, what we now collectively call the Second Plague Pandemic. Given that we have increasing reason to include much of Eurasia and Africa in our narratives of the Second Plague Pandemic, not just Europe, it is time to rethink what data is relevant for tracking this disease across various landscapes. As the paleogenetic data for plague’s history grows, so, too, does the need to newly interrogate our traditional sources of historical information. Digitization projects of libraries and archives are making the written historical record accessible in ways hitherto unimaginable, and archaeological projects are likewise creating a new corpus of data for reconstructing the material and cultural remains of societies, even in the absence of written records. On the assumption that a digital humanities (DH) approach is key to developing a consilient, interdisciplinary collaboration and a new kind of collective evidentiary platform, this exploratory seminar will gather together the leading plague researchers in the world—from genetics, archaeology, and history—along with DH specialists, to discuss what a Second Plague Pandemic archive should look like, and what the best means will be to create a platform that can be used by multiple disciplines simultaneously.