The World Health Organization’s (WHO) response to COVID-19 highlighted the challenges of managing a global health crisis within existing international frameworks and tensions between political pressures and managerialism. The International Health Regulations (2005) (IHR) proved inadequate in preventing the rapid spread of the virus, leading WHO to take unprecedented reactive and strategic measures and underscoring the urgency and gravity of the situation. These actions included, inter alia, the aggressive use of its epistemic authority, the establishment of new governance tools, and the creation of global technical hubs. This chapter examines how the WHO Secretariat, particularly under the leadership of its Director-General Dr Tedros Adhanom Ghebreyesus, undertook these measures, often without explicit mandates granted by its governing bodies, to respond to the COVID-19 pandemic as well as trying to improve prevention, preparedness, and response capacities for future health emergencies, and to fight the inequitable distribution of power in the access to life-saving medical countermeasures.