The death toll from it has yet to reach 100, but an outbreak of swine flu has gotten huge amounts of attention in the media in recent weeks. Even though regular flu viruses have killed thousands in that time, swine flu is all over the news because of worry that it could escalate into a pandemic, which is an outbreak of infectious disease across a large geographical area. There are countless instances of mass pandemics in history, and some have even been powerful enough to topple governments and nearly wipe out whole civilizations. Chances are that swine flu will run its course and soon be forgotten, but here are 10 examples of diseases that have made a huge mark on history.

10. The Plague Of Athens

The Plague of Athens was an epidemic that broke out in Greece during the Peloponnesian War in 430 BC. Historians have been unable to agree on exactly what the plague was, with typhoid, smallpox, and measles all being considered, but it is most commonly considered to have been a form of the bubonic plague. The disease started when the inhabitants of Athens retreated behind the city-state’s walls for protection from the approaching Spartan army. The cramped quarters inevitably became a breeding ground for the plague, which is said to have killed one in three of the city-state’s inhabitants, including its leader, Pericles.

9. Malaria

Although it is now mostly confined to the tropics, malaria is still one of the world’s most devastating pandemics, and continues to infect as many as 500 million people every year. The sickness, which is caused by a parasite found in certain mosquitoes, is  resistant to drugs, and a dependable vaccine has still yet to be developed. Malaria and its effects have been well documented as a major factor throughout history. There were over a million cases of the disease during the American Civil War alone, and malaria is considered by many to have been a factor in the decline and eventual fall of the Roman Empire.

8. The Antonine Plague

Now suspected to have been an outbreak of measles or smallpox, the Antonine Plague was a pandemic that ravaged the Roman Empire from 165 to 180 AD. Also known as the Plague of Galen, the disease is suspected to have been brought to Rome by troops returning from battle. It is estimated that at its height the Antonine Plague killed a quarter of all the people it infected, as many as 5 million in all, and victims included two of Rome’s emperors. In 251 AD, a similar sickness broke out, which many believe to have been a return of the Plague of Antonine. This time it was known as the Plague of Cyprian, and at its height it is said that the disease was killing 5,000 people a day in the city of Rome.

7. Typhus

Known for its ability to spread quickly in cramped and unsanitary conditions, typhus is credited with millions of deaths in the 20th century alone. The disease is also known as “camp sickness” for the way it seems to flare up on the front lines during wartime. It is said that 8 million Germans were killed by a typhus pandemic during the 30 years war, and the disease is also well documented as a significant cause of death in Nazi concentration camps. Typhus is perhaps most famously known for nearly wiping out the French army during Napoleon’s invasion of Russia. It has been estimated that as many as 400,000 of his soldiers may have died from the disease, many more than were killed in combat.

6. The 7 Cholera Pandemics

One of the most consistently dangerous diseases in history, cholera and its so-called “seven pandemics” killed millions between 1816 and the early 1960s. Generally transmitted through contaminated food or drinking water, the disease first sprang up in India, where it is said to have killed as many as 40 million between 1817 and 1860. It would soon spread to Western Europe and the United States, where it killed more than a hundred thousand people in the mid-1800s. Since then, there have been periodic outbreaks of cholera, but advances in medicine have made it a much less deadly disease. While it once had a mortality rate of 50 percent or more, when treated cholera is now life threatening only in the most rare of cases.

5. The Third Pandemic

The Third Pandemic was the third major outbreak of the bubonic plague, following the Plague of Justinian and the Black Death. It started in China in the 1850s, and would eventually spread to all six inhabited continents before tapering off sometime in the 1950s. Despite modern breakthroughs in medicine, the Third Pandemic still killed as many as 12 million people in China and India, and though it is now considered inactive, as recently as 1995 a number of isolated cases of the disease were discovered in the western United States.

4. Smallpox

Although it has since been successfully eradicated, smallpox devastated the Americas when European settlers first introduced it in the 15th century. Of all the diseases brought to the new world, smallpox was the most virulent, and it is credited with the deaths of millions of native peoples in the United States and Central America. Smallpox decimated the Aztec and Incan civilizations and is generally considered to be a major factor in their eventual conquering by the Spanish. The disease was equally dangerous back in Europe, where it is estimated to have killed 60 million people in just the 18th century alone.

3. The Plague of Justinian

Generally regarded as one of the first pandemics in the historical record, The Plague of Justinian was a particularly virulent disease that broke out in the Byzantine Empire around 541 AD. Although the exact numbers are uncertain, the plague is estimated to have caused the deaths of 100 million people worldwide–5,000 a day at its peak–and it is regarded to have killed at least one in four people in the eastern Mediterranean region. Beyond this staggering mortality rate, the political effects of the Plague of Justinian were far-reaching, as its devastation prevented the Byzantine Empire from being able to spread eastward into Italy and thus significantly changed the course of European history.

2. The Spanish Flu

Arriving on the heels of the devastation of World War I, the Spanish Flu of 1918 is widely considered to be one of the most vicious pandemics in history. A worldwide phenomenon, it is estimated to have infected one third of the world’s entire population, and eventually killed as many as 100 million people. The virus, which has since been identified as a strain of H1N1, would surface in waves, frequently disappearing in communities as quickly as it arrived. Fearing a massive uproar, governments did their best to downplay the severity of the flu, and because of wartime censorship, its far-reaching effects were not fully realized until years later. Only Spain, a neutral country during WWI, allowed comprehensive news reporting on the pandemic, which is why it eventually became known as the Spanish Flu.

1. The Bubonic Plague (The Black Death)

Perhaps the most well known pandemic in history, the Black Death was a massive outbreak of bubonic plague that ravaged Europe through most of the 1300s. Characterized by the appearance of oozing and bleeding sores on the body and a high fever, the plague is estimated to have killed anywhere from 75 to 200 million people in the 14th century alone, with recent research concluding that 45-50% of the entire population of Europe was wiped out. The Plague would be a constant threat for the next hundred years, periodically resurfacing and killing thousands, with the last major outbreak occurring in London in the 1600s.

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