Wherever bacteria are found, so are the viruses that infect them. These viruses, called bacteriophages are the most abundant biological entities on Earth. To initiate an infection, phages bind to specific bacterial surface proteins or cell wall components to inject their genetic material into the cell. To prevent infection by bacteriophages, bacteria have developed an arsenal of defense mechanisms. Restriction-Modification Systems contain two major components: a restriction endonuclease and a methyltransferase. CRISPR-Cas systems are comprised of a DNA-based array of clustered regularly interspaced short palindromic repeats and CRISPR-associated genes that enable antiphage function. Bacteriophage genomes are modified by a wide variety of chemical modifications. Nuclease activation is the other major target for known anti-CRISPR mechanisms.