Microbial communities are spatially organized in both the environment and the human body. Although patterns exhibited by these communities are described by microbial biogeography, this discipline has previously only considered large-scale, global patterns. By contrast, the fine-scale positioning of a pathogen within an infection site can greatly alter its virulence potential. In this Review, we highlight the importance of considering spatial positioning in the study of polymicrobial infections and discuss targeting biogeography as a therapeutic strategy.