Osteosarcoma is the most common malignant bone tumor affecting children and adolescents. Currently, the most common treatment is surgery combined with neoadjuvant chemotherapy. Although the survival rate of patients with osteosarcoma has improved in recent years, it remains poor when the tumor (s) progress and distant metastases develop. Therefore, better animal models that more accurately replicate the natural progression of the disease are needed to develop improved prognostic and diagnostic markers, as well as targeted therapies for both primary and metastatic osteosarcoma. The present review described animal models currently being used in research investigating osteosarcoma, and their characteristics, advantages, and disadvantages. These models may help elucidate the pathogenic mechanism (s) of osteosarcoma and provide evidence to support and develop clinical treatment strategies.