Global threats to public health in the 19th century sparked the development of international health diplomacy. Many international regimes on public health issues were created between the mid-19th and mid-20th centuries. The present article analyses the global risks in this field and the international legal responses to them between 1851 and 1951, and explores the lessons from the first century of international health diplomacy of relevance to contemporary efforts to deal with the globalization of public health.