Life-sustaining treatment (LST) is any treatment that serves to prolong life without reversing the underlying medical condition, and includes cardiopulmonary resuscitation, mechanical ventilation, haemodialysis, left ventricular assist devices, antibiotics, and artificial nutrition and hydration. The appropriate use of LST in seriously ill patients is a controversial topic that continues to generate intense debate amongst private citizens as well as health-care professionals, bioethicists, lawyers, governments, and religious institutions. This chapter sets out important questions clinicians ought to consider before making the decision to withhold or withdraw LST. This practical guide should enable clinicians to accurately identify the issues relevant to a given case and to make decisions that are both medically and ethically sound.