Acquired immunodeficiency syndrome (AIDS) emerged as an epidemic in Africa in 1981, and now it has become a most destructive global pandemic. Human immunodeficiency virus (HIV) is responsible for the pathogenesis of AIDS, and it is usually transmitted through unsafe sexual activities. HIV is a lentivirus that can remain latent in the host cells for a long period, and it has various mechanisms to establish latency. The HIV genome encodes several microRNAs (miRNA-TAR, miRNA-H1, miRNA-H3, and miRNA-Nef-367) that act as posttranscriptional control by targeting mRNA sequences. The miRNA-TAR, miRNA-Nef-367, and miRNA-H1 have established roles in HIV latency, whereas miRNA-H3 can activate the latent reservoirs of HIV. The human genome also encodes several miRNAs that have defensive roles against infections. Cellular miRNAs (miRNA-29a, miRNA-146a, miRNA-34c-5'p, miRNA-186, miRNA-210 and miRNA-222) also contribute to viral latency. The most challenging hurdle in the development of effective HIV therapeutics is viral latency. A complete understanding of latency will enable us to develop efficient therapeutics and to eradicate HIV from the globe.