Oftentimes, patients at the end of life may present with challenging symptoms refractory to conventional therapies. Agitation and terminal restlessness, 2 common symptoms encountered in the hospice population, are frequently managed using benzodiazepines or typical antipsychotics. In clinical scenarios that either preclude their use or in which they prove ineffective, alternative pharmacotherapy must be considered. Propofol, a sedative-hypnotic unrelated to any other class of drug, may provide palliation of agitation and terminal restlessness refractory to benzodiazepines or antipsychotics. Here, the authors present a hospice patient admitted to the general medical floor of a small community hospital for pain and symptom management. A history of polysubstance abuse contributes to rapidly escalating doses of opioids and midazolam. Failure to control her symptoms resulted in the initiation and successful titration of propofol.