Current osteosarcoma chemotherapy is “standard” (doxorubicin, cisplatin, high-dose methotrexate ± ifosfamide-mesna, and etoposide ± mifamurtide), but current regimens have many short-term, medium-term, and long-term side effects. Generally 12–15 cycles of chemotherapy are given in the hospital over 7–10 months. Even in the absence of new research protocols, improvement in quality of life is now possible, with all osteosarcoma chemotherapy agents now being able to be administered in the outpatient setting. Outpatient chemotherapy is not only less expensive, but in the adolescent and young adult population can result in better quality of life for some. This paper shares information to help reduce the frequency of hospitalization and review some tools and strategies to facilitate communication when providing outpatient chemotherapy, family-centered care, and information/education.