In recent years, microRNAs (miRNAs) have emerged as a major class of regulatory genes, present in most metazoans and important for a diverse range of biological functions. Because experimental identification of miRNA targets is difficult, there has been an explosion of computational target predictions. Although the initial round of predictions resulted in very diverse results, subsequent computational and experimental analyses suggested that at least a certain class of conserved miRNA targets can be confidently predicted and that this class of targets is large, covering, for example, at least 30% of all human genes when considering about 60 conserved vertebrate miRNA gene families. Most recent approaches have also shown that there are correlations between domains of miRNA expression and mRNA levels of their targets. Our understanding of miRNA function is still extremely limited, but it may be that by integrating mRNA and miRNA sequence and expression data with other comparative genomic data, we will be able to gain global and yet specific insights into the function and evolution of a broad layer of post-transcriptional control.