Tumor progression during end-of-life care can lead to significant pain, which at times may be refractory to routine analgesic techniques. Although regional anesthesia is commonly used for postoperative pain care, there is limited experience with its use during home hospice care. We present a 24-year-old male with end-stage metastatic osteosarcoma who required anesthetic care for a right-sided above-the-elbow amputation. The anesthetic management was complicated by the presence of a large mediastinal mass, limited pulmonary reserve, and severe chronic pain with a high preoperative opioid requirement. Intraoperative anesthesia and postoperative pain management were provided by regional anesthesia using an interscalene catheter. He was discharged home with the interscalene catheter in place with a continuous local anesthetic infusion that allowed weaning of his chronic opioid medications and the provision of effective pain control. The perioperative applications of regional anesthesia in palliative and home hospice care are discussed.