Palliative care and hospice should be the standards of care for all terminally ill patients. The first place for clinicians to go when responding to a request for assisted death is to ensure the adequacy of palliative interventions. Although such interventions are generally effective, a small percentage of patients will suffer intolerably despite receiving state-of-the-art palliative care, and a few of these patients will request a physician-assisted death. Five potential “last resort” interventions are available under these circumstances: (1) accelerating opioids for pain or dyspnea; (2) stopping potentially life-prolonging therapies; (3) voluntarily stopping eating and drinking; (4) palliative sedation (potentially to unconsciousness); and (5) physician-assisted death. Patient, family, and clinicians should search for the least harmful way to respond to intolerable end-of-life suffering in ways that are effective and also respect the values of the major participants. A system that allows an open response to such cases ultimately protects patients by ensuring a full clinical evaluation and search for alternative responses, while reinforcing the need to be responsive and to not abandon.