Between 2016 and 2020 the Australian government established a regional health security diplomacy project, known as the Indo–Pacific Centre for Health Security. In light of the COVID-19 pandemic, the initiative looked prescient. Its roots, however, could be traced back to Australia’s engagement with health security in the early 2000s. Then, as now, the government aligned its foreign policy agenda with health – specifically emerging infectious diseases – as a ‘scaled up’ approach comprising diplomatic, aid, and research and development. To explain Australia’s evolving relationship with health security this chapter proceeds in four parts. First, health security is situated with the recent tradition of ‘non-traditional security’. The second part examines the establishment of health security as a core theme in Australia’s response to global challenges. The third part turns to the government’s strategy and especially the Indo–Pacific Centre for Health Security both before and during the COVID-19 era. Finally, the chapter examines how Australia conceptualised its leadership role in regional health security.