Pentobarbital (previously known as pentobarbitone in Britain and Australia) is a short-acting barbiturate typically used as a sedative, a preanesthetic, and to control convulsions in emergencies. It can also be used for short-term treatment of insomnia but has been largely replaced by the benzodiazepine family of drugs.

In high doses, pentobarbital causes death by respiratory arrest. It is used for veterinary euthanasia and is used by some U.S. states and the U.S. federal government for executions of convicted criminals by lethal injection. In some countries and states, it is also used for physician-assisted suicide.

Pentobarbital was widely abused and sometimes known as "yellow jackets" due to the yellow capsule of the Nembutal brand. Pentobarbital in oral (pill) form is no longer commercially available.