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The development of microarray technology has allowed the genomes of mycobacteria to be directly compared to identify
DNA
regions that differ between strains due to deletion, insertion, or sequence divergence. The use of microarrays in comparative genomics has proved to be a valuable tool for comparing both mycobacterial species and strains. We describe here the methodology for comparing two mycobacterial DNA samples by microarray hybridization, from labeling and slide preparation, to DNA microarray analysis options. Further developments in microarray design and methodology promise to ensure that microarrays remain an important resource for comparative genomic studies in the future.