The Black Death came from Central Asia. It struck China first, then India, spreading west to the Middle East and Europe. It traveled along the trade routes inside fleas on rats and humans. In October 1347, when a Genoese galley full of dying men arrived in Messina, Italy from the Crimea, no one at first realized the danger. Then, people in the city began to take sick. They suffered swellings in the armpits and groin, dying within three days. Or they took a high fever, spitting blood, dying less than a day later. Some went to bed apparently well and never woke up.
The plague spread throughout Europe, sparing only a few areas, like Hungary, for reasons still unclear. No one knows the total death toll, though most historians agree that at least a third of the population of Europe alone died. Crowded areas where the plague could spread from human to human like towns, cities and monasteries suffered the worst, losing over half of their population. Entire villages and even regions were left desolate, their ruins sinking back into the earth before the plague finally abated in 1351.
Worse yet, the plague did not come unannounced. It followed a series of famines beginning in 1315, brought on by bad weather. This was the Little Ice Age which lasted from the mid-14th until the 19th century. During this cold period, the plague returned every generation (about twenty years) until the Great Plague of London in 1665.
Many have tried to explain the Black Death. Medieval physicians thought it "bad air" from earthquakes or living near swamps. Since the highest mortalities occurred in large cities, which were usually founded on rivers, this seemed to make sense. In the 19th century, scientists settled on Bubonic Plague, which struck Constantinople in the 6th century and is endemic in North Africa today, as the culprit. But recently, other scientists have suggested a hemorrhagic fever similar to Ebola, a virus deadlier than bird flu. Either way, scientists and historians don't know why it started and, more importantly, why it left.
Or when it might return.