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Tuberculosis (TB) is an ancient disease with an enormous global impact. Despite declining global incidence, the diagnosis, phenotyping, and epidemiological investigation of TB require significant clinical microbiology laboratory resources. Current methods for the detection and characterization of Mycobacterium tuberculosis consist of a series of laboratory tests varying in speed and performance, each of which yields incremental information about the disease. Since the sequencing of the first M. tuberculosis genome in 1998, genomic tools have aided in the diagnosis, treatment, and control of TB. Here we summarize genomics-based methods that are positioned to be introduced in the modern clinical TB laboratory, and we highlight how recent advances in genomics will improve the detection of antibiotic resistance-conferring mutations and the understanding of M. tuberculosis transmission dynamics and epidemiology. We imagine the future TB clinic as one that relies heavily on genomic interrogation of the M. tuberculosis isolate, allowing for more rapid diagnosis of TB and real-time monitoring of outbreak emergence.