The veterinary profession has a unique responsibility to animals during the final stages of their lives. The veterinarian's obligations extend to humane endings, involving all species of animals in a range of circumstances including, but not limited to, euthanasia of individually owned animals, euthanasia of animals for research purposes, depopulation of animals during emergencies, and slaughter of animals raised for food. The veterinary profession continues to improve animal welfare through advances in end-of-life decision-making and humane killing techniques,1-3 but the psychological impacts on veterinarians have not received the same level of consideration. Building on the influential AVMA Humane Endings Guideline, the AVMA recognizes that support for the mental health of veterinarians engaged in such activities needs to be a priority. This article aims to provide the foundation and rationale for improved preparation and establishment of sustainable mental health resources and to offer recommendations on pragmatic solutions to support and prepare veterinary professionals as leaders impacted by participation in humane endings-related activities. While end-of-life decision-making and implementation may present mental health challenges to veterinarians, it is crucial to recognize that there are stressors specific to each situation and that every individual's experience is valid. Addressing the mental health issues surrounding the decision-making process and implementation of humane endings activities start with a comprehensive understanding of each activity's unique context and the veterinarian's leadership role. Therefore, this article highlights the psychological impact of depopulation and its similarities and exclusive challenges compared with euthanasia and humane slaughter.