MicroRNAs represent a large family of non-coding small RNAs that function as the major endogenous triggers for RNA interference. Hundreds of microRNAs have been identified through small RNA cloning, bioinformatic predictions, and high-throughput pyrosequencing. They are believed to suppress gene expression through post-transcriptional regulation via either translational repression or mRNA turnover. Over one third of human genes are predicted targets for microRNAs. However, even after extensive studies, the function of microRNAs and the precise mechanism by which they suppress gene expression remain elusive. Although controversy remains, recent advances have shined new light on how microRNAs regulate their targets. A better understanding of the mechanism should facilitate studies of their function.