During the past two decades, a number of variable genetic sequences have been uncovered that permit molecular typing of Mycobacterium tuberculosis complex (MTC) organisms. Since the determination of the M. tuberculosis, and later M. bovis, genome sequences, the nature of these variable genetic sequences has become more evident, permitting a clearer recognition of which molecular tools lend themselves best to certain applications. In this review, ‘classical’ genotyping methods for molecular epidemiologic uses are briefly discussed, followed by a more detailed description of post-genomic typing methods, including large sequence polymorphisms otherwise referred to as genomic deletions. Because genomic deletions represent unique event polymorphisms not prone to reversion, these mutations effectively ‘brand’ bacterial lineages, including species/subspecies of the MTC and specific clades of M. tuberculosis sensu stricto. Genomic deletions therefore provide a new opportunity to accurately classify organisms for diagnostic and epidemiologic purposes, serving as the basis for further study of the natural variability across MTC organisms.