ABSTRACTOsteosarcoma, the most common primary malignant tumor of bone, occurs frequently in teenagers and is the third most common type of cancer among children and adolescents. Osteosarcoma originates from malignant mesenchymal stem cells. Fibroblasts, osteoblasts, osteoclasts, and immune cells, among other cell types, are present in the osteosarcoma microenvironment and work in conjunction to regulate osteosarcoma tumorigenesis. Extracellular vesicles (EVs) are spherical bilayer-membrane vesicles released by cells into extracellular spaces and body fluids, including plasma and synovial fluid. EV cargos contain various biomolecules, such as DNA, mRNAs, non-coding RNAs, proteins, lipids, and metabolites. EVs mediate intercellular communication by delivering these bioactive molecules to recipient cells and play a critical role in maintaining cellular homeostasis and promoting pathological progression. A growing body of evidence indicates that EVs play an important role in osteosarcoma tumorigenesis. In this review, we discuss existing knowledge on the important roles of tumor-derived or microenvironment-derived EVs in tumorigenesis, development, metastasis, drug resistance, and communication with the osteosarcoma microenvironment. We propose the potential of EVs in osteosarcoma diagnosis and treatment.HighlightsExtracellular vehicles play crucial function in osteosarcoma tumorigenesis.Extracellular vehicles mediated the intercellular communication of osteosarcoma cells with other types cells in tumor microenvironment.Extracellular vehicles have potential utility in osteosarcoma diagnosis and treatment.