Stroke can produce irreversible brain damage of massive proportion leading to severe disability and poor quality of life. Resuscitation and mechanical ventilation of these patients remain controversial because of the high mortality and severe disability involved. When prognosis is very poor, do-not-resuscitate orders (DNR orders) and withhold or withdrawal of treatment may be discussed. Studies have shown that DNR orders are relatively frequent in acute stroke: up to 30% of all patients, and 50% of which are given upon admission. DNR orders are closely associated with severity of the neurological deficit and age. Precise estimates of withhold and withdrawal of treatment are not available, but terminal extubations in severe stroke could contribute to 40,000 to 60,000 acute stage deaths per year. Little is known about the decision making process and palliative care in these situations. The neurological prognosis is the main explicit criterion. However, evaluation of neurological outcome is highly uncertain and difficult, and does not always reflect quality of life. Several studies have raised the issue of this disability paradox. Thus, physician estimation of prognosis has a profound impact on decisions for life sustaining therapies, and may lead to self-fulfilling prophecies in case of false appreciation of published evidence. Other criteria could influence the withhold and withdrawal of treatment decision, such as social conditions and patient values. Decisions for life-sustaining therapies in severe stroke are always difficult and often based on subjective and uncertain criteria. We have to improve prognosis estimation and our understanding of patient preferences to promote patient-centered care. An ethical approach may guide these complex decisions.