The results of several studies suggest that alterations in various cell cycle regulatory genes are involved in the pathogenesis of osteosarcomas. Experiments in animal models provide preliminary data on the feasibility of gene therapy in osteosarcoma and chondrosarcoma. Prediction of response to chemotherapy remains a major focus of imaging research. Several clinicopathologic studies have explored the mechanisms underlying multidrug resistance in osteosarcoma patients receiving neoadjuvant chemotherapy. HER2/erbB2 expression, linked to poor prognosis, has been proposed as a therapeutic target in osteosarcoma. In clinical studies of osteosarcoma, further data confirm the activity of ifosfamide and carboplatin but provide little support for the use of immunotherapy. A retrospective analysis showed no value for dose intensification of doxorubicin/cisplatin, but the results of a prospective trial should be more informative. Recent evidence confirms that secondary osteosarcomas and malignant fibrous histiocytomas of bone should be treated with aggressive chemotherapy regimens, similar to those used for osteosarcomas.