Chronic infections often contain complex mixtures of pathogenic and commensal microorganisms ranging from aerobic and anaerobic bacteria to fungi and viruses. The microbial communities present in infected tissues are not passively co-existing but rather actively interacting with each other via a spectrum of competitive and/or cooperative mechanisms. Competition versus cooperation in these microbial interactions can be driven by both the composition of the microbial community as well as the presence of host defense strategies. These interactions are typically mediated via the production of secreted molecules. In this review, we will explore the possibility that microorganisms competing for nutrients at the host–pathogen interface can evolve seemingly cooperative mechanisms by controlling the production of subsets of secreted virulence factors. We will also address interspecies versus intraspecies utilization of community resources and discuss the impact that this phenomenon might have on co-evolution at the host–pathogen interface.