Despite the intense effort put by researchers globally to understand Human Immunodeficiency Virus (HIV-1) pathogenesis since its discovery 30 years ago, the acquired knowledge till date is not good enough to eradicate HIV-1 from an infected individual. HIV-1 infects cells of the human immune system and integrates into the host cell genome thereby leading to persistent infection in these cells. Based on the activation status of the cells, the infection could be productive or result in latent infection. The current regimen used to treat HIV-1 infection in an AIDS patient includes combination of antiretroviral drugs called Highly Active Anti-Retroviral Therapy (HAART). A major challenge for the success of HAART has been these latent reservoirs of HIV which remain hidden and pose major hurdle for the eradication of virus. Combination of HAART therapy with simultaneous activation of latent reservoirs of HIV-1 seems to be the future of anti-retroviral therapy; however, this will require a much better understanding of the mechanisms and regulation of HIV-1 latency. In this chapter, we have tried to elaborate on HIV-1 latency, highlighting the strategies employed by the virus to ensure persistence in the host with specific focus on epigenetic regulation of latency. A complete understanding of HIV-1 latency will be extremely essential for ultimate eradication of HIV-1 from the human host.