Osteosarcoma is the most common type of primary bone tumor in adolescents and young adults. The dysregulation of cell cycle control and cell division often results in the aberrant growth of osteosarcoma cells. The primary proteins involved in cell cycle control and cell division include checkpoint kinases (CHKs), cyclin-dependent kinases (CDKs), polo-like kinases (PLKs) and aurora kinases (AURKs). In recent years, a large number of these protein kinase inhibitors have been identified in osteosarcoma. In this review, we highlight the current drugs being developed to target these protein kinases in osteosarcoma.