Sarcomas are malignant solid tumors of mesenchymal origin which consist of 10-15% of all pediatric malignancies and associated with significantly high mortality rates despite current therapies. Oncogenic fusion genes, resulting from non-random chromosomal translocations, characterize a subset of sarcomas including rhabdomyosarcoma, the Ewing's sarcoma family of tumors, and synovial sarcoma. As investigators gain further insight into the role that fusion genes play in the development and progression of sarcomas, we are slowly uncovering novel molecules and pathways that are proving to be essential for the growth and maintenance of sarcomas and other malignancies. MicroRNAs (miRs) have been implicated in a diversity of human diseases including cancer. Only recently, has miR deregulation been shown to be an important component of sarcomagenesis. This review summarizes the recent discoveries tying miR deregulation to sarcoma biology and will discuss the potential and feasibility of miRs as novel therapeutic adjuncts to current therapies. The methodological approaches utilized in the study of miR biology and development of miR-based treatment regimens can serve as a paradigm for future investigations in other translocation-associated solid tumors.