Osteosarcoma remains one of the most common bone cancers in children and adolescents. While conventional therapy can be effective at reducing or stabilizing primary osteosarcoma tumors, metastatic disease is typically refractory to treatment. Cytotoxic T-lymphocytes (CTL) likely play an important role in the control of developing metastatic osteosarcoma as polymorphisms in the inhibitory tumor necrosis factor receptor (TNFR) family member, cytotoxic T lymphocyte antigen 4 (CTLA4) that result in increased protein expression levels are associated with higher risk of developing osteosarcoma. We have investigated the role of PD-1, another inhibitory TNFR family member, in limiting the efficacy of CTL to mediate metastatic osteosarcoma immune control. We show that human metastatic, but not primary, osteosarcoma tumors are expressing PD-1 and that tumor infiltrating CTL express PD-1, suggesting this pathway limits CTL control of metastatic disease in patients. PD-L1 is also expressed on K7M2 tumor cells that establish metastatic disease in mice, and PD-1 is expressed on tumor infiltrating CTL during disease progression. Blockade of PD-1/PD-L1 interactions in the K7M2 mouse model of metastatic osteosarcoma dramatically improves survival outcomes by enhancing the function of osteosarcoma-specific CTL. These results suggest that blockade of PD-1/PD-L1 interactions in patients with metastatic osteosarcoma should be pursued as a means of improving prognosis in children.