Proportionate sedation in pediatric palliative care (PPC) is an important therapy for refractory symptom management. Standard therapies have been successfully employed in this regard for decades. However, there remains a subset of patients for which symptoms prove refractory even to standard therapies. There is an evolving literature base describing the role of non-standard sedative and anesthetic agents in the management of the most complex and refractory symptoms. This chapter explores both the principles and the practice of proportionate sedation for symptoms refractory to standard therapies in pediatric palliative care.