MicroRNAs (miRNAs) regulate many developmental processes, but despite the numerous miRNA-mRNA interactions that have been bioinformatically predicted,few miRNA targets have been experimentally confirmed. Now, on p. 3043, Min Han and colleagues present a systematic analysis of these interactions during C. elegans development. Using a previously established immunoprecipitation approach, they have found that distinct sets of miRNAs and their target mRNAs are present at five different developmental stages. Although most mRNAs targeted by miRNAs are continuously and stably regulated throughout development, ∼28% of them, the authors report, display complex temporal changes. Interestingly, developmental miRNA regulation predominantly affects genes involved in cell signalling, whereas housekeeping genes are largely unaffected, and at least some of the miRNA regulation preferences are stage dependent. Thus, the authors propose, subsets of miRNAs might orchestrate developmental events by coordinately targeting or avoiding genes involved in specific biological processes. This study also yields important insights into the rules of physiological target recognition by miRNAs, which should benefit future studies in this field.