Eukaryotic small RNA comprises several classes of 21–25 nucleotide non-coding RNA, of which microRNA (miRNA) has gained a great deal of attention because it is directly involved in controlling growth and development in plants. miRNAs are processed by the RNase III-like Dicer, although recent studies have implicated additional gene products in the step-wise maturation of miRNAs from their primary nuclear transcripts. They function as sequence-specific guides to trigger cleavage or translational repression of target mRNAs that have complementary sequences. Natural miRNA targets encode members of large families of transcription factors, which are collectively required for a number of developmental processes. In addition to developmental regulation, some miRNAs might be involved in specific physiological responses to several types of stresses, such as those induced by pathogen infections. Strikingly, the potyviruses, the largest group of plant RNA viruses, are able to interfere with miRNA-guided cleavage of multiple regulatory targets in plants, thus modulating gene expression of the host cell.