Although microRNA (miRNA)-mediated functions have been implicated in many aspects of animal development, the majority of miRNA::mRNA regulatory interactions remain to be characterized experimentally. We used an AIN/GW182 protein immunoprecipitation approach to systematically analyze miRNA::mRNA interactions during C. elegans development. We characterized the composition of miRNAs in functional miRNA-induced silencing complexes (miRISCs) at each developmental stage and identified three sets of miRNAs with distinct stage-specificity of function. We then identified thousands of miRNA targets in each developmental stage, including a significant portion that is subject to differential miRNA regulation during development. By identifying thousands of miRNA family-mRNA pairs with temporally correlated patterns of AIN-2 association, we gained valuable information on the principles of physiological miRNA::target recognition and predicted 1589 high-confidence miRNA family::mRNA interactions. Our data support the idea that miRNAs preferentially target genes involved in signaling processes and avoid genes with housekeeping functions, and that miRNAs orchestrate temporal developmental programs by coordinately targeting or avoiding genes involved in particular biological functions.