Palliative sedation therapy (PST) is an important clinical intervention for pediatric patients with refractory symptoms and suffering during the end-of-life (EOL) period. Variations in PST implementation including medication selection, limited literature regarding feasibility in various clinical settings, particularly non-intensive care units, and lack of education on evolving definitions and ideal practices may all contribute to the current underutilization of this valuable resource. We therefore offer a clinical algorithm for identifying appropriate patients for PST, ensuring all other modalities for symptom management have been considered and/or optimized, and present a guideline for PST implementation that can be adapted and individualized based on institutional experience and resource availability. Furthermore, through case-based clinical scenarios, we demonstrate how to incorporate this algorithm into EOL practice.