Palliative care is a discipline that provides satisfactory symptom relief to most patients with advanced life-threatening disease. There remain circumstances, however, in which patients experience distressing symptoms and unbearable suffering that cannot be adequately relieved. In these situations palliative sedation may be valuable as a last resort. Palliative sedation is a controversial issue and research in this area is complex for ethical and practical reasons. A review of some critical aspects, giving special attention to those areas that require further research, is therefore timely.There is a dearth of evidence regarding sedation in the setting of palliative care. The literature contains many expert opinions and retrospective reports, but only a few prospective studies have been published. Terminology regarding sedation is confusing, indications and outcomes do not tend to be clearly reported, and no comparative studies to test drug effectiveness have been conducted. Consensus and innovative methodologies to enhance scientific knowledge are urgently needed in this area.This review addresses recent literature concerning definitions of palliative sedation and intolerable/refractory suffering, indications and drug use. The current state of the art is summarized and future lines of research are proposed.