Bacterial growth and survival in numerous environments are constrained by the action of bacteria-consuming protozoa. Recent findings suggest that bacterial adaptations against protozoan predation might have a significant role in bacterial persistence and diversification. We argue that selective predation has given rise to diverse routes of bacterial defense, including adaptive mechanisms in bacterial biofilms, and has promoted major transitions in bacterial evolution, such as multicellularity and pathogenesis. We propose that studying predation-driven adaptations will provide an exciting frontier for microbial ecology and evolution at the interface of prokaryotes and eukaryotes.