In October 2001, three seminal papers, reproduced in their entirety in this booklet, appeared in the same issue of Science, together solidifying the evidence for an intriguing form of RNA. Named, by mutual agreement, microRNAs (miRNAs), these single-stranded small RNA molecules were isolated simultaneously by the three laboratories. Novel forms of knockout and knockdown animals are now being developed in which regions of DNA coding for miRNAs are being deleted or their expression reduced, respectively. The resulting aberrant phenotypes are unexpectedly broad and variable. The knowledge gained from these experiments—and the implication of miRNAs in several human disease pathologies—points to promising opportunities for therapeutic intervention through the targeting of miRNAs.