The current state of the science in the fields of patient safety and palliative and end-of-life care have many issues in common. This article synthesizes recent systematic reviews and additional research on improving patient safety and end-of-life care and compares each field's perspective on common issues, both in traditional patient safety frameworks and in other areas, and how current approaches in each field can inform the other. The article then applies these overlapping concepts to a key example area: improving documentation of patient preferences for life-sustaining treatment. The synthesis demonstrates how end-of-life issues should be incorporated into patient safety initiatives. In addition, evaluating overlap and comparable issues between patient safety and end-of-life care and comparing different perspectives and improvement strategies can benefit both fields.