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. Since the recognition of DNA methylation being important in Escherichia coli and bacteriophage resistance using restriction/modification systems, more than 43,600 restriction enzymes have been cataloged in more than 3600 different bacteria. While DNA sequencing methods have made great advances there is a dearth of method advances to examine these modifications in situ. However, the large increase in whole genome sequences has led to advances in defining the modification status of single genomes as well as mining new restriction enzymes, methyltransferases, and modification motifs. These advances provide the basis for the study of pan-epigenomes, population-scale comparisons among pangenomes to link replication fidelity and methylation status along with mutational analysis of mutLS. Newer DNA sequencing methods that include SMRT and nanopore sequencing will aid the detection of DNA modifications on the ever-increasing whole genome and metagenome sequences that are being produced. 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.