Osteosarcoma (OSA) is the most common primary bone tumor diagnosed in dogs. Our understanding of the risk factors and genetic changes in canine OSA patients is growing, but specific, innovative therapeutic strategies are slow in coming. Appendicular skeletal osteosarcoma, the most frequent form of this disease, is typically seen in large to giant breeds, with males being overrepresented in most reports. Axial skeletal OSA is less common than appendicular OSA, but the biologic behavior of the disease is equally aggressive in all skeletal sites except for the mandible. Though the current standard of care for dogs with osteosarcoma remains surgical resection of the affected site, followed by chemotherapy with either a platinum- (cisplatin or carboplatin) or doxorubicin-based protocol, novel therapies are being actively investigated.