Osteosarcoma (OS), the most common primary malignant bone tumor in both children and adults, is characterized by the development of bone or osteoid substance by the tumor cells [1]. Despite of Surgical treatments and combinational chemotherapy, long term survival remains unsatisfactory because of delay in diagnosis, distant metastasis and chemoresistence. Thus, in recent years, it has become one of the most promising fields to investigate molecular mechanisms contributing to osteosarcoma carcinogenesis and progression. Several biomarkers have been proposed to predict the evolution of osteosarcoma including survivin, ErbB2, Ki67 antigen, alpha V integrins, Tumor Endothelial Marker (TEM7), IGF1, Leptin, micro RNA. Recent advances in expression biology have shifted in identifying and developing specific and sensitive biomarkers such as micro RNAs. Circulating micro RNA is emerging as promising noninvasive biomarkers for human cancers. In this review,we provide a perspective on emerging concepts and potential usefulness of microRNA as diagnostic, prognostic markers in OS and involvement of specific microRNA in OS metastasis. We tried to discuss the genetic mechanisms and molecular pathways involved by aberrant microRNA in OS. MiRNA-directed gene regulation will pave the way for improving traditional gene therapy approaches in many cancers. Moreover, since therapeutic targeting of miRNAs promises to improve the clinical management of patients with OS.