Elucidation of the molecular basis of disease depends upon continued progress in defining the mechanisms by which genomic information is encoded and expressed. Transcription factor-mediated regulation of mRNA is clearly a major source of regulatory control and has been well studied. The more recent discovery of small RNAs as key regulators of gene function has introduced a new level and mechanism of regulation. Mammalian genomes contain hundreds of microRNAs (miRNAs) that each can potentially downregulate many target genes. This suggests a new source for broad control over gene regulation and has inspired extensive interest in defining miRNAs and their functions. Here, the identification of miRNAs, their biogenesis, and some examples of miRNA effects on biology and disease are reviewed and discussed. Emphasis is placed on the possible role for miRNA in nervous system development, function, and disease.