Chapter 6 explores to the ways Ottoman subjects and Western Europeans residing in the Middle East contended with actual plague epidemics and argues that Western conceptions of plague informed their broader evaluations of the Ottoman Empire. The chapter examines how easily diplomatic conundrums filtered into the casual discourse of travelers and how closely medical and political evaluations were intertwined. Plague helps open up the Eastern Question by making clear how the political dilemmas it posed were not the exclusive purview of high diplomacy but were deeply implicated in medical and cultural perceptions of the “East.” It was possible, we see, for Western Europeans to construct the presence of plague as a central civilizational dividing line even as Ottoman and Western responses to the disease were relatively similar.