MicroRNAs (miRNAs) are abundant approximately 22-nucleotide regulatory RNAs encoded in animal genomes. They are thought to exhibit diverse biological functions in animals by targeting messenger RNAs (mRNAs) for degradation or translational repression. Here we use T-cell development as a model to illustrate methods and strategies for dissecting the post transcriptional gene regulatory networks controlled by miRNAs and their roles in the differentiation of T-cell precursors. The process involves the identification of miRNA genes in rare T-cell progenitors, determining miRNA expression during T-cell development, characterizing miRNA function in T-cell development using an in vitro assay, and identifying functionally relevant gene(s) regulated by miRNAs.