MicroRNAs (miRNAs) are tiny genetic rheostats in plants, animals, and viruses, regulating the expression of messenger RNAs by targeting transcripts for cleavage or translational repression. Their regulatory impact is even more pervasive as a potential therapeutic tool. Since inception, computational methods have been an invaluable tool complementing experimental approaches. Here, we outline miRNA-bioinformatics highlighting the biological and therapeutic repertoire of miRNAs, in silico prediction of miRNA genes and their targets, along with a glimpse of the bioinformatic challenges that lie ahead. (C) 2007 Elsevier Inc. All rights reserved.