Crop diseases, in conjunction with climate change, are a major threat to global crop production. DNA methylation is an epigenetic mark and is involved in plants’ biological processes, including development, stress adaptation, and genome evolution. By providing a new source of variation, DNA methylation introduces novel direction to both scientists and breeders with its potential in disease resistance enhancement. Here, we discuss the impact of pathogen-induced DNA methylation modifications on a host's transcriptome reprogramming and genome stability, as part of the plant's defense mechanisms. We also highlight the knowledge gaps that need to be investigated for understanding the entire role of DNA methylation in plant pathogen interactions. This will ultimately assist breeders toward improving resistance and decreasing yield losses.