Bacteriophages, viruses that infect bacteria, play a pivotal role in microbial communities by driving ecological and evolutionary processes. Their rapid and intimate coevolution with bacterial hosts—driven by both vertical and horizontal evolution—has led to the remarkable diversity of phages observed today. Both phages and phage proteins such as phage lysins and phage depolymerases are studied as non-traditional antibacterial modalities as a response to the aggravating antimicrobial resistance crisis. We study the evolutionary processes driving the diversity of phages and their proteins and we mimic these processes on a bench scale to engineer phages and their proteins to powerful antibacterials customized to their application.