Genome methylation in bacteria is an area of intense interest because it has broad implications for bacteriophage resistance, replication, genomic diversity via replication fidelity, response to stress, gene expression regulation, and virulence. Increasing interest in bacterial DNA modification is coming about with investigation of host/microbe interactions and the microbiome association and coevolution with the host organism. While DNA sequencing methods have made great advances there is a dearth of method advances to examine these modifications in situ. As more sequences become available, larger analyses are being done to provide insight into the role and guidance of bacterial DNA modification to bacterial survival and physiology.