Pluripotent stem cells (PSCs) express a distinctive set of microRNAs (miRNAs). Many of these miRNAs have similar targeting sequences and are predicted to regulate downstream targets cooperatively. These enriched miRNAs are involved in the regulation of the unique PSC cell cycle, and there is increasing evidence that they also influence other important characteristics of PSCs, including their morphology, epigenetic profile and resistance to apoptosis. Detailed studies of miRNAs and their targets in PSCs should help to parse the regulatory networks that underlie developmental processes and cellular reprogramming.