Canine osteosarcoma (OS) is an aggressive tumour that accounts for approximately 90% of primary bone tumours in the dog. Although the standard treatments (including limb amputation/sparing, chemotherapy and palliative radiotherapy) have significantly increased survival rates, almost 90% of animals will eventually develop predominantly pulmonary metastases. Despite advances in various therapies, prognosis remains poor, with median survival times ranging from 3 months to 1 year and <20% of dogs survive for >2 years following diagnosis. Various clinical and epidemiological markers have facilitated decision-making with respect to therapy but no single molecular biomarker has been shown to enhance prediction of disease progression. The publication of the canine genome in 2005 raised the possibility of increasing understanding of the genetic mechanisms underpinning canine OS. This review explores the use of biomarkers within the multi-disciplinary management of dogs with OS, and highlights the few known, potential prognostic/predictive molecular markers including their potential value as 'bridging biomarkers' for human OS. Although high-throughput profiling of canine OS remains in its infancy, research within the next decade using leading-edge screening technologies has the potential to identify biomarkers that may enhance diagnostic and prognostic accuracy and result in more effective, individually tailored, treatment and management protocols for affected dogs.