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Formalin is commonly thought to decrease the risk of Mycobacterium tuberculosis infection. However, the true disinfection efficacy of formalin for tissue infected with M tuberculosis is unclear. We reviewed all pertinent literature from 1900 until the present regarding the disinfection efficacy of formalin for tissue infected with M tuberculosis. We also retrospectively cultured five cases of M tuberculosis from formalin-fixed archival pulmonary tissue. All cultures from our archived tissue were negative. The literature review revealed limited and contradictory information concerning the viability of M tuberculosis in formalin-fixed human tissue. There are no studies which specifically address the viability of M tuberculosis in tissue exclusively fixed in 10% buffered formalin. The disinfection efficacy of formalin for tuberculosis infected tissue remains unclear. Larger, prospective studies using current methodologies are needed to establish guidelines to ensure the safety for those handling infected, fixed tissue.