This paper argues that epidemics and other calamities occurring across the Ottoman Empire contributed more than political and military factors to the fall of the Ottomans in World War I. Historians have generally given little attention to natural or environmental phenomena as factors affecting the political development of the Ottoman Empire. Recently, a number of studies have approached the history of the eastern Mediterranean from an environmental perspective. So far, the role of disease, famines, and other calamities in the rise of the Empire in the fourteenth century seems clear: the plague, an urban disease, devastated the Byzantines, but it did little harm to the early Ottomans, nomads who were constantly on the move. Yet the part such disasters played in the downfall of the Empire is yet to be explained. In this paper, I shall attempt to do just that, using a broad range of evidence, from Ottoman archival documents through Arab and Turkish chronicles to European accounts. The Ottomans, who for long refused to adopt quarantine to contain plague outbreaks, began to make extensive use of it in the 1830s. Yet by the 1850s European nations trading in the Mediterranean had already abandoned this method. With the developing understanding of sanitation, hygiene, and the discovery of bacteria, quarantine seemed useless. It was replaced by stricter health policies. From the 1850s to the 1890s, European nations exerted pressure on the Ottomans to give up quarantine – a policy that harmed trade in the Mediterranean – but the latter, for various internal considerations, refused to do so. The Ottoman approach to containing disease finally shifted from a contagionist understanding of epidemics to an infectionist one in the early 1890s, from which point quarantines were used less frequently. But it was too little, too late. A series of severe cholera outbreaks in the military and within civilian populations that state health authorities could not contain, accompanied by famine and earthquakes, had weakened the Empire significantly during the Russo-Ottoman War of 1877-78 and the Balkan Wars of 1912-13. By the time the Ottomans entered the Great War in 1914, the state’s ability to mobilize troops and rely on its cities and citizens for supplies and support had become very limited. Outdated health practices bred military failures, which ultimately led the Ottomans to their defeat in the War.