microRNAs (miRNAs) are an abundant class of newly identified endogenous non-protein-coding small RNAs. They exist in animals, plants, and viruses, and play an important role in gene silencing. Translational repression, mRNA cleavage, and mRNA decay initiated by miRNA-directed deadenylation of targeted mRNAs are three mechanisms of miRNA-guided gene regulation at the post-transcriptional levels. Many miRNAs are highly conserved in animals and plants, suggesting that they play an essential function in plants and animals. Lots of investigations indicate that miRNAs are involved in multiple biological processes, including stem cell differentiation, organ development, phase change, signaling, disease, cancer, and response to biotic and abiotic environmental stresses. This review provides a general background and current advance on the discovery, history, biogenesis, genomics, mechanisms, and functions of miRNAs.