© 2022 by Pediatric Infectious Diseases and Immunization Society.Diphtheria has long been related to epidemics and has been one of the primary causes of death among children. The discovery and widespread use of diphtheria antitoxin at the end of the nineteenth century resulted in significant reductions in the fatality rate. The discovery of a diphtheria toxoid vaccine in the early 1920s led to a drop in epidemics, and the World Health Organization’s introduction of the Expanded Program on Immunization in 1971 resulted in a more than 90% reduction in diphtheria cases. However, diphtheria outbreaks continue to occur around the world due to factors such as wars, migration, and vaccine hesitancy, which result in a drop in immunization coverage. Diphtheria epidemics were common in the Ottoman Empire around the end of the nineteenth and beginning of the twentieth centuries. Diphtheria antitoxin production began in the empire in 1895, a notification mandate was introduced with the issued regulations and circulars, and detailed instructions were provided for the steps to be followed for the diagnosis, treatment, and control of the disease. Preventive services were prioritized in the early days of the Republic, and the Refik Saydam Institute of Hygiene and Public Health was established for vaccine production and diagnostic work, as well as the School of Public Health for personnel training. With the dissemination of health service provision, the execution of the Expanded Program on Immunization, and the continuance of effective immunization with all its components, diphtheria, which caused 4999 cases and 661 deaths recorded in 1958, has had zero instances notified since 2011.