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Background Palliative sedation therapy (PST) is used to treat refractory symptoms at the end of life. Phenobarbital is infrequently used as a third-line agent following unsuccessful symptom control with first-line and second-line agents. However, there is wide clinical and guideline variance in the use of phenobarbital, reflecting a gap in the literature.Objective The aim of this study is to summarise the current evidence and guidelines surrounding practices of phenobarbital use in PST and discuss areas for future investigations, specifically regarding route of administration, time to death, dosing and concurrent use of first-line and second-line PST.Methods Studies and guidelines on the use of phenobarbital in PST were retrieved from PubMed and Google and the reference list of identified papers through to August 2024.Key findings Limited case studies and retrospective audits have been conducted into the use of phenobarbital in PST. These studies and existing guidelines reflect a degree of variance specifically regarding recommendations about route of administration, dosing and use of first-line and second-line PST. Efficacy is not well reported. However, phenobarbital use appears to be safe and does not appear to impact time to survival.Conclusion Phenobarbital appears to have a safe and potentially efficacious role as a third-line agent in PST. Great variance exists with regards to optimal dosing and the concurrent use of first- and second-line PST agents. High-quality research and multicentre reviews are required to enhance the understanding of optimal phenobarbital use and encourage evidence-based practice in palliative medicine.