Long non-coding RNAs (lncRNAs) with more than 200 nuleotides, have been explored to participate in various cancer types including osteosarcoma (OS), which is the most common kind of primary bone tumors with high morbidity in infants and adolescents. These oncogenic or tumor suppressive lncRNAs regulate OS pathogenesis, such as cell growth, proliferation, invasion, migration, metastasis and cell apoptosis, serve as independent prognostic biomarkers or play a significant role in multidrug resistance (MDR) in OS cells. In this review, we attempt to dissect the participation of lncRNAs in pathogenesis of OS and their potential clinical values, and also provide an outlook for viable biomarkers and therapeutic targets in OS.