On the eve of the plague in 1346, people began to see a decline in the period of the High Middle Ages as populations were declining because of famines. There were economic problems as well as several Italian banks had gone under, and with them the dreams of enterprising traders and town-builders. Yet, trade was still an important part of European society and the Italian cities of Genoa and Venice profited most significantly from new markets and new products. Unfortunately, these new trade routes were key in bringing to Europe from the far reaches of Asia (nobody knows exactly where the plague first began) the worst epidemic of plague Christendom had ever known.

The bubonic plague, caused by a bacterium called Yersinia pestis, is said to have killed from 30-50% of the European population; up to two thirds of the population of many of the major European cities succumbed to the plague in the first two years. There was hardly a generation which did not experience a local, regional or pan-European epidemic for the next two hundred years. This recurring plague killed off a large percentage of children born between infestations of plague and dampened economic and demographic growth until the late seventeenth century. There were attacks on women lepers and Jews who were thought either to have deliberately spread the plague or, because of their “innate dishonor”, to have polluted society and brought on God's vengeance. The violence against outsiders demonstrated the nature and the limits of citizenship in Europe. This was a society which defined itself as Christian and recurrent plague changed religious practice, if not belief. Christians had long venerated saints as models of godly life and as mediators before God, in this case an angry and vengeful one. A whole new series of "plague saints" (like St. Roch) came into existence along with new religious brotherhoods and shrines dedicated to protecting the population from plague.

The plague also affected several other aspects of European life, including the economy, and intellectual changes. Intellectually, plague stimulated chroniclers, poets and authors, and physicians to write about what might have caused the plague and how the plague affected the population at large. Boccaccio's Decameron is one of the most famous of the writings. Also, the recurrence of plague affected the general understanding of public health. Beginning in Italy in the 1350s, there were new initiatives aimed at raising the level of public sanitation and governmental regulation of public life. By the sixteenth century a debate over the causes of plague spread in the medical community as old corruption theories inherited from Greece and Rome were replaced by ideas of contagion. The plague also affected the economy as the population decrease caused by the plague led to an economic depression. Merchants and tradespeople had fewer people to whom they could sell their wares. Products therefore accumulated, and the merchants and traders suffered a loss in income. Economic hardship spread throughout the community as those who dealt with the merchants--bankers, suppliers, and shippers--also lost revenue. As incidences of the plague decreased in the late fifteenth century, populations swelled, creating a new demand for goods and services. A new middle class began to emerge as bankers, merchants, and tradespeople once again had a market for their goods and services. Some people were able to take economic advantage of the situation and of the numerous deaths occurring. People called the beccamorti [literally vultures], who provided their service in dragging dead bodies away, were paid such a high price that many were enriched by it. Many died from carrying away the dead , some rich, some after earning just a little, but high prices continued.

After the plague, allowed servants to have greater control over their wages and their conditions of working as there weren’t enough workers to technically run the farms (one way in which feudalism declined; there literally weren’t enough people to be running the farms). Public events were greatly monitored and curtailed; events such as weddings or even funerals. The reason why it was necessary to put a brake on weddings was because when they gathered for the betrothal, each party brought too many people in order to increase the pomp, which increased the chances of possibly getting the plague again. Some of the restrictments were how many days were necessary for the funeral and how many women took part in a woman’s wedding.