Zoonotic diseases, caused by pathogens transmitted to people from vertebrate reservoirs, take an enormous toll on human health worldwide. Many of these disease agents are harbored in rodent populations, and humans are victims of “accidental” transmission. Here we explore the idea that predatory vertebrates indirectly protect human health by reducing population size of rodent reservoirs of human disease. Research frontiers include the importance of rodent population density to the incidence of human disease, as opposed to behavior or age structure effects; the roles of different types of predators in determining both population dynamics and rodent density per se; and the effects of human-caused environmental change on predators and their rodent prey. A better understanding of these basic ecological issues will inform both environmental and health policy.