Background: Nurses play an integral role in providing care for patients with end of life (EOL) symptoms refractory to conventional treatments and that may necessitate palliative sedation (PS). A paucity of research on nurses' attitudes, knowledge, and experience with PS exists, despite nurses being instrumental in evaluating its appropriateness and carrying out the care plan. Objective: The objective of the study was to elicit nurses' perspectives and conceptualizations of knowledge and skills needed to administer PS in order to inform development of a hospital policy that addresses identified concerns. Methods: Four focus groups were conducted with nurses likely to have had exposure to PS (oncology, intensive care, and hospice) at an academic medical center. Focus groups were audiotaped, transcribed verbatim, and coded for salient themes. Grounded theory principles were used for the analysis. Results: Among the four focus groups (n = 31), 87% were female, 58% between the ages of 36 and 55, and more than 40% reported 10-plus years of providing patient care. Five domains emerged as important in developing a PS policy: 1) ability to define PS; 2) criterion for using PS; 3) skill set for administering PS; 4) policy and procedural guidelines; and 5) education on PS and EOL care. Conclusions: Nurses identified knowledge, skills, and guidelines as key considerations for implementing PS. Comprehensive policies along with adequate training are needed to expand the availability of PS in acute care hospitals and hospice programs.