Cellular restriction of HIV-1 replication has traditionally been thought of as protein mediated: APOBEC3G hypermutates HIV-1 genomic RNA, but is counteracted by Vif; Tetherin inhibits the release of budding virions but is counteracted by Vpu. In recent years, new evidence suggesting that miRNAs and other components of the miRNA pathway act as HIV-1 restriction factors has come to light, along with the identification of strategies that HIV-1 employs to surmount these host obstacles. In this article, we summarize and discuss the literature to date regarding the complex relationship between HIV-1 and miRNA-mediated inhibition.