Pandemic cholera had a complex and transformative impact on medicine, the science of sanitation and hygiene, and broader sociopolitical developments in Iran during the Qajar era. This paper will show how cholera changed Iranian perspectives on governance, unmasked social and political vulnerabilities, and caused enduring institutional changes during this critical time in the country’s development. Specifically, this paper will explain the role of the 1889-1892 cholera epidemics in cementing the role of Shi‘ite clerics against Western encroachment and government exploitation. It will also shed light on how the 1904 cholera outbreak shifted popular perspectives in favor of the germ theory of diseases and the central government’s sanitary responsibilities to its people. Using a number of Persian language period newspapers, this paper will show how the popularity of microbialism gave rise to the anti-establishment rhetoric of the Constitutional Revolution and ensuing changes in Iran's vaccination culture.