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TB is a deadly disease\u2010causing maximum death per year due to a single infectious agent. In the case of TB, there is an urgent need for novel host\u2010directed therapies which can effectively target the survival and long\u2010term persistence of the bacteria without developing drug resistance in the bacterial strains while also reducing the duration and toxicity associated with the mainstream anti\u2010TB drugs. Recent studies have suggested that TB infection has a significant effect on the host epigenome thereby manipulating the host immune response in the favor of the pathogen. <jats:italic>M.tb<\/jats:italic> alters the activation status of key genes involved in the immune response against TB to promote its survival and subvert the antibacterial strategies of the host. These changes are reversible and can be exploited to design very efficient host\u2010directed therapies to fight against TB. 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