Concern grows daily over the spread of highly pathogenic avian influenza (HPAI) across the globe. We call for three measures to radically lower the risk of a new influenza pandemic: (i) improved wildlife, agricultural, and human sampling for One Health surveillance; (ii) accelerated implementation of new indoor air engineering standards (American Society of Heating, Ventilating, and Air-conditioning Engineers [ASHRAE] Standard 241) and associated research on agent fate to significantly lower the potential for human respiratory infection; and (iii) continued investments in animal and human vaccines, along with improved public health communication that address the mechanisms of health disinformation campaigns. Given the stakes, it’s imperative that we act quickly.