Despite recognition of the health threat posed at the human-animal-environment interface long ago, One Health has yet to be meaningfully integrated into global pandemic prevention, preparedness, and response. With the negotiation of the forthcoming pandemic instrument under the auspices of the World Health Organization (WHO) — which is inherently restricted by its own constitutional mandate of human health — One Health risks being sidelined once again. Genuine integration of a One Health approach into this treaty will require the institutionalization of formal One Health coordination mechanisms.