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The Nigeria Centre for Disease Control (NCDC) is Nigeria's first public health agency with the mandate to protect the health of Nigerians from the threat and occurrence of infectious diseases. Following a change in leadership in August 2016, the agency had been on a journey of transformation into a public health institute that was able to assure the health security of Nigerians. Dr Chikwe Ihekweazu, its Director General and the change leader, joined the organisation in August 2016 by the appointment of Nigeria's President Muhammadu Buhari, having worked extensively in the area of public health in the United Kingdom, Germany and South Africa. Along with his team, his priority was to ensure that NCDC evolved into a public health institute that was well equipped, both in terms of material resources and people, to respond to diseases of public health importance, effectively. The case describes the change efforts, the challenges and the successes and ends with a question on the sustainability of the change initiatives in an increasingly dynamic world.