MicroRNAs (miRNAs) are endogenous short noncoding RNA molecules (20 – 23 nucleotides) that regulate cell differentiation, cell proliferation, and apoptosis through post-transcriptional suppression of gene expression by binding to the complementary sequence in the 3' untranslated region (3'UTR) of target messenger RNAs (mRNAs) (1). Hundreds of miRNAs have been identified in humans and they are evolutionarily conserved (1, 2). In addition, the presence of up to 1000 miRNAs is estimated by computational analysis (3). Strikingly, 30% of protein-encoding genes in humans are predicted to be regulated by miRNAs (4). Recently, it has been revealed that altered expression of specific miRNA genes contributes to the initiation and progression of diseases such as cancer (5 – 10). This review focuses on the biogenetic and functional mechanisms and the involvements in cell differentiation and cancer in mammalian miRNAs and the utility of miRNAs in drug discovery.