While writers on bioethics regularly assume or argue that patient autonomy must and will prevail when conflicts arise between patients and caregivers about proposed courses of therapy, in actual practice there exists a major challenge to autonomy, particularly in end-of-life decision-making. Medical futility represents the judgment of physicians and health care institutions that a particular course of treatment is not indicated for medical reasons and may be refused to the patient or his proxy, despite the fact that it is desired and even insisted on by them. Futility policies have as one of their goals to provide a way to say “no” to particular exercises of autonomy by patients, proxy decision makers, and family. While patients retain the right to seek a transfer of care to other physicians and institutions when possible, the original professionals need not relent and offer therapy if such a transfer cannot be arranged. Medical futility is not well understood by physicians and is virtually unknown to the public and prospective patients. It combines clinical judgments of therapeutic efficacy with value judgments about the worthwhileness of the sort of life that can be secured by the therapy. In this paper I will assess the concept of futility and its usefulness and role in end of life decision-making.