MicroRNAs (miRNAs) are key posttranscriptional regulators of gene expression involved in diverse biological pathways in bilateral animals and plants. The key to understanding the biological function of a miRNA is to identify its regulatory targets. Although a few miRNA targets have been identified genetically, the rapidly expanding list of miRNAs has necessitated genome-wide tools for identifying target mRNAs, and a number of computational and experimental approaches have consequently emerged. Some of these approaches have also provided insights into the mechanistic aspects of miRNA-mediated regulation, another intensely debated area in the miRNA field. Here, we review several emerging features of miRNA–target interactions in animals and genome-wide approaches for probing those interactions.