microRNAs (miRNAs) form an evolutionarily conserved and highly abundant class of non-coding RNAs that are 21-24 nucleotides (nt) in length. They are processed from double-stranded (ds) RNA precursors and sequence-specifically guide posttranscriptional gene silencing. The processing steps are facilitated by members of the RNAse III enzyme family, whereas gene silencing events are mediated by members of the highly conserved Argonaute (Ago) protein family. Initially discovered in Caenorhabditis elegans, in which they are essential for proper developmental timing, hundreds of miRNAs have been discovered to date in a variety of different organisms, including plants, flies and mammals. Expression profiling approaches demonstrated that miRNAs are specifically expressed not only during embryonic development, but also during cell differentiation and other cellular events such as hormonal signaling. Although miRNAs have been the object of extensive research in recent years, very little is known about their target mRNAs. Their identification along with a comprehensive description of the miRNA/target-mRNA interaction network will add a new level to our knowledge of gene regulation and will also provide new insights into the biology of so far poorly understood diseases, including various forms of cancer.