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A myriad of methods has been reported for the isolation of genomic
DNA
from
Mycobacterium
spp.; some methods use mechanical disruption of the bacterial cells, whereas others use some form of chemical or enzymatic lysis. Regardless of the approach, the end points remain efficient breaking of the complex mycobacterial cell wall and release of high-quality DNA that is suitable for manipulation and analyses by molecular genetic techniques. This chapter providers detailed methods for the large and small isolation of mycobacterial genomic DNA.