Osteosarcoma (OS) is the most common primary bone tumour in children and adolescents, with high degree of malignancy and an extremely poor prognosis. Ferroptosis, a non-traditional mode of regulated cell death (RCD) characterised by iron-dependent accumulation of lipid reactive oxygen species (ROS), is closely associated with a variety of cancers. It has been demonstrated that ferroptosis can regulate OS progression and exert an essential role in the treatment of OS, which is potentially of great value. By targeting ferroptosis in OS, the present review article summarises the relevant mechanisms and therapeutic applications along with discussing current limitations and future directions, which may provide a new strategy for the treatment of OS.© 2021 The Author(s).