MicroRNAs (miRNAs) are major drivers of cell fate specification and differentiation. The post-transcriptional regulation of key molecular factors by microRNAs contributes to the progression of embryonic and postembryonic development in several organisms. Following the discovery of lin-4 and let-7 in Caenorhabditis elegans and bantam microRNAs in Drosophila melanogaster, microRNAs have emerged as orchestrators of cellular differentiation and developmental timing. Spatiotemporal control of microRNAs and associated protein machinery can modulate microRNA activity. Additionally, adaptive modulation of microRNA expression and function in response to changing environmental conditions ensures that robust cell fate specification during development is maintained. Herein, we review the role of microRNAs in the regulation of differentiation during development.