Liposomal muramyl tripeptide phosphatidyl ethanolamine (L-MTP-PE) is a synthetic biological investigational agent used for treating osteosarcoma. It has been used in both canine and human osteosarcoma to reduce pulmonary metastases, the most common pattern of treatment failure for sarcomas. L-MTP-PE has been well tolerated using the concept of biological cancer therapy during chemotherapy. The use of L-MTP-PE with ifosfamide is the best studied combination with single agent chemotherapy. This may represent a new treatment choice for osteosarcoma patients receiving ifosfamide. Such patients include those with a poor initial histological response to primary therapy and/or metastatic disease including pulmonary metastases. Reduction of side effects of L-MTP-PE, such as fever and/or flu-like symptoms, with ibuprofen has not reduced efficacy. Since improved symptom control is possible using drug combinations that are especially effective for delayed nausea, outpatient high-dose ifosfamide chemotherapy combined with L-MTP-PE may lead to a safe and effective therapy while maintaining the patients' quality of life.