Context. Guidelines about palliative sedation typically include recommendations to protect the well-being of relatives. Objectives. The aim of this study was to systematically review evidence on the experiences of relatives with the practice of palliative sedation. Methods. PubMed, Embase, Web of Science, PsycINFO, and CINAHL were searched for empirical studies on relatives' experiences with palliative sedation. We investigated relatives' involvement in the decision-making and sedation processes, whether they received adequate information and support, and relatives' emotions. Results. Of the 564 studies identified, 39 were included. The studies (30 quantitative, six qualitative, and three mixed methods) were conducted in 16 countries; three studies were based on relatives' reports, 26 on physicians' and nurses' proxy reports, seven on medical records, and three combined different sources. The 39 studies yielded a combined total of 8791 respondents or studied cases. Caregivers involved relatives in the decision making in 69%-100% of all cases (19 quantitative studies) Conclusion. Relatives' experiences with palliative sedation are mainly studied from the perspective of proxies, mostly professional caregivers. The majority of relatives seems to be comfortable with the use of palliative sedation; however, they may experience substantial distress by the use of sedation. J Pain Symptom Manage 2012;44:431-445. (C) 2012 U. S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.