Aversive responses toward elements of the natural world, termed biophobias, are widespread. Whether they involve an irrational fear of animals, plants, germs, or dark forests, biophobias have far-reaching consequences that remain largely unstudied outside psychology and psychiatry. Foremost, biophobias affect mental health and entail direct (e.g., healthcare) and indirect (e.g., absenteeism from work) costs. In addition, they contribute to environmental and health issues through the overuse of pesticides and sanitizers, hinder sustainability efforts (e.g., insect phobia as a barrier to adopting insects in Western diets), and incur nonmaterial costs such as cultural erosion and avoidance of nature. Because these impacts emerge from complex interactions between human societies and ecosystems, we argue that biophobias are a quintessential One Health issue. One Health thinking could guide research and policy efforts to integrate medical, socioeconomic, and ecological perspectives in addressing biophobias. To advance a One Health agenda for biophobias, key knowledge gaps urgently need to be addressed.