Sodium pentobarbital and pentobarbital combination products are commonly used by veterinarians throughout the US for euthanasia of their animal patients. The AVMA Guidelines for the Euthanasia of Animals: 2020 Edition lists barbiturate acid derivatives (pentobarbital) and pentobarbital combination products as an acceptable method of euthanasia for all species when circumstances permit their use. When using pentobarbital products, a veterinarian must consider appropriate handling and disposal of animal remains to avoid the potential for environmental contamination, relay toxicosis in wildlife or domestic animals, and contamination of the animal food supply. Failure to appropriately consider these facets of pentobarbital euthanasia can result in legal and ethical consequences. Despite these concerns, to the authors’ knowledge no comprehensive literature review has been published concerning pentobarbital euthanasia or handling and disposal of animal remains following pentobarbital euthanasia. The literature review that follows aims to give a descriptive narrative of the most recent information available on the knowledge, use, challenges, and issues surrounding pentobarbital euthanasia and disposal of animal remains within the US.