Osteosarcoma is an aggressive malignancy that usually occurs in children and young adults, and long-term survival is only about 20% in patients with metastasis or recurrent disease. Traditional non-invasive techniques, such as positron-emission tomography (PET) scanning, magnetic resonance imaging (MRI) or computed tomography (CT) scanning, may not identify single lesions in the early stage or accurately detect small lesions. A novel technique, positron emission tomography/computed tomography (PET/CT), which is widely used in clinical practice, shows more accuracy, sensitivity, and specificity in the diagnosis of osteosarcoma. PET/CT provides information not only for diagnosis of primary lesion and metastases, but also for histological response to neoadjuvant chemotherapy and prognosis. Here, we review the role of PET/CT in the diagnosis and prognosis of osteosarcoma.