The majority of plants are able to form the arbuscular mycorrhizal (AM) symbiosis in association with AM fungi. During symbiosis development, plant cells undergo a complex reprogramming resulting in profound morphological and physiological changes. MicroRNAs (miRNAs) are important components of the regulatory network of plant cells. To unravel the impact of miRNAs and miRNA-mediated mRNA cleavage on root cell reprogramming during AM symbiosis, we carried out highthroughput (Illumina) sequencing of small RNAs and degradome tags of Medicago truncatula roots. This led to the annotation of 243 novel miRNAs. An increased accumulation of several novel and conserved miRNAs in mycorrhizal roots suggest a role of these miRNAs during AM symbiosis. The degradome analysis led to the identification of 185 root transcripts as mature miRNA and also miRNA*-mediated mRNA cleavage targets. Several of the identified miRNA targets are known to be involved in root symbioses. In summary, the increased accumulation of specific miRNAs and the miRNA-mediated cleavage of symbiosis-relevant genes indicate that miRNAs are an important part of the regulatory network leading to symbiosis development.Small silencing RNAs are a complex group of short RNAs with sizes in the range of approximately 20 to 25 nucleotides in length that can regulate gene expression at the transcriptional and posttranscriptional levels (Bartel, 2004;He and Hannon, 2004). In recent years, it has become evident that two main classes of small silencing RNAs, short interfering RNAs and microRNAs (miRNAs), are of great importance in plants. Small RNAs are involved in developmental processes, hormonal signaling, organ polarity, RNA metabolism, and abiotic and