Bacteria and the viruses that infect them, bacteriophages, are locked in a fierce coevolutionary battle. The need to defend themselves against phages has driven bacteria to evolve sophisticated immunity mechanisms, including restriction-modification and CRISPR systems. More recently, it has become clear that there are many additional immunity mechanisms in bacteria. Using a powerful new functional selection, we have identified dozens of new anti-phage systems. Through in-depth studies of several of these systems, we are beginning to elucidate how bacteria both sense and respond to phage infection, with striking parallels to the mechanisms used by mammalian cells to sense and respond to their viral and bacterial predators.