Mycobacterium tuberculosis (MTB) has co-evolved with humans for decades and developed several mechanisms to evade host immunity. It can efficiently alter the host epigenome, thus playing a major role in immunomodulation by either activating or suppressing genes responsible for mounting an immune response against the pathogen. Epigenetic modifications such as DNA methylation and chromatin remodelling regulate gene expression and influence several cellular processes. The involvement of epigenetic factors in disease onset and development had been overlooked upon in comparison to genetic mutations. It is now believed that assessment of epigenetic changes hold great potential in diagnosis, prevention and treatment strategies for a wide range of diseases. In this review, we unravel the principles of epigenetics and the numerous ways by which MTB re-shapes the host epigenetic landscape as a strategy to overpower the host immune system for its survival and persistence.