Background: Palliative sedation (PS) involves the administration of sedative medications and analgesics with the purpose of reducing level of consciousness for patients with refractory suffering in the setting of imminent dying and terminal illness. Although the merits of PS, as well as potential concerns, have been raised frequently in the literature in the past two decades, the clinical utilization and acceptance of PS (and of palliative care in general) have been sparse in Mexico. Discussion: As a relatively new treatment option for medical care providers in Mexico, palliative care and the appropriate use of PS are being slowly and cautiously introduced into clinical practice. However, acceptance of the ethical, moral, and legal permissibility of PS remains variable, as is the understanding of appropriate use or integration of palliative care into clinical practice in Mexico. Summary: Given changes to Mexican law that have called for provision of adequate palliative care for all patients in Mexico, and advance care planning laws that allow patients to refuse medical treatments that are not consistent with their goals of care, this paper seeks to frame commonly articulated positions regarding PS, explores these challenges in Mexico, and suggests putative guidelines for safe and appropriate implementation of PS. At the urging the Ministry of Health in Mexico, we present a cogent, evidence-based, and internationally vetted protocol outlining the indications for PS and suggested clinical practice guidelines for safe and effective implementation of PS in Mexico for appropriate patients.