Plague is an important zoonotic bacterial disease, and a cause of significant mortality in wild rodents and rabbits. In some animals such as prairie dogs, outbreaks may kill nearly all of the animals in a colony. Sporadic cases also occur in other wild and domesticated mammals, particularly felids. Infections in animals can be transmitted to humans, resulting in life-threatening disease. Pneumonic plague, which is a particularly deadly form of the disease, is usually fatal if antibiotics are not started very soon after the symptoms appear. Bubonic plague, the most common form, is less fulminant, but also has a high mortality rate if left untreated.

At least three major plague pandemics have been seen in human populations. The Justinian plague occurred in the Mediterranean region in the 6th century AD and caused an estimated 100 million deaths, and the Black Death killed a third of the European population beginning in the 14th century. The most recent pandemic, which began in China in the late 1800s, spread worldwide and caused an estimated 12 million fatalities by 1930. The organisms that caused these three pandemics still exist in wild animal reservoirs in parts of the world, and occasionally spill over from these reservoirs to affect people or other animals. More than a thousand human cases and 100 to 200 deaths are reported annually to the World Health Organization (WHO), and many additional cases are probably not diagnosed. Most outbreaks occur in Asia and Africa, but sporadic cases and outbreaks can be seen in any endemic region. Plague may reoccur after a long period when the disease seems to disappear; recent outbreaks in India, Indonesia and Zambia followed quiescent periods of 30 to 50 years. An additional concern is that the agent of plague has been identified as a potential biological weapon.