MicroRNAs are small RNA molecules of 20-22 nucleotides, initially discovered in Caenorhabditis elegans, and involved in the regulation of various biological processes in plant and mammalian systems. Essentially, they are key gene regulators as they may inhibit gene expression by mRNA degradation or inhibiting mRNA translation. The identification of microRNAs in plant and human viruses raised important questions regarding their function and potential use as antiviral targets. Reports have described microRNAs encoded by HIV and also the involvement of cellular mRNA in the course of HIV infection. This review investigates the potential use of microRNAs in therapeutic strategies against HIV infection and their role for the eradication of viral reservoirs.