During their co-evolution with pathogens, hosts acquired defensive health strategies that allow them to maintain their health or promote recovery when challenged with infections. The cooperative defense system is a largely unexplored branch of these evolved defense strategies. Cooperative defenses limit physiological damage and promote health without having a negative impact on a pathogen’s ability to survive and replicate within the host. Here, we review recent discoveries in the new field of cooperative defenses using the model pathogens Citrobacter rodentium and Salmonella enterica. We discuss not only host-encoded but also pathogen-encoded mechanisms of cooperative defenses. Cooperative defenses remain an untapped resource in clinical medicine. With a global pandemic exacerbated by a lack of vaccine access and a worldwide rise in antibiotic resistance, the study of cooperative defenses offers an opportunity to safeguard health in the face of pathogenic infection.