Africa’s borderlands face considerable difficulties in controlling the spread of COVID-19. It is essential that these territories receive a targeted response, in line with the core commitment of the 2030 Sustainable Development Agenda to ‘leave no one behind’. The serious threat posed by the disease – and the urgency of the response – is most apparent in its spread to areas of intractable insecurity, such as the Chad Basin, borderlands in the Sahel, and the Mandera Triangle between Kenya, Somalia, and Ethiopia. If action is taken fast, strategies developed in close cooperation with borderland communities could still mitigate the worst of the outbreak. This research and policy brief identifies key structural vulnerabilities in borderlands, as well as opportunities for the disease response to generate lasting change.